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Sample records for advanced non-small cell

  1. Crizotinib for Advanced Non-Small Cell Lung Cancer

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    A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

  2. Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

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    Shu-Hui Yao

    2016-03-01

    Full Text Available Objective: To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer. Methods: A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected. Results: Progressionfree survival and median overall survival (mOS of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05; 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05, and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05. Conclusions: Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

  3. Effects of icotinib on advanced non-small cell lung cancer with different EGFR phenotypes.

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    Pan, Huiyun; Liu, Rong; Li, Shengjie; Fang, Hui; Wang, Ziwei; Huang, Sheng; Zhou, Jianying

    2014-09-01

    Icotinib is the first oral epidermal growth factor receptor (EGFR) tyrosine kinase receptor inhibitor, which has been proven to exert significant inhibitory effects on non-small cell lung cancer in vitro. Clinical evidence has showed that the efficacy of Icotinib on retreating advanced non-small cell lung cancer is comparable to Gefitinib. However, different phenotypes of EGFR can affect the therapeutic outcomes of EGFR tyrosine kinase receptor inhibitor. Therefore, our study focused on efficacy and safety of Icotinib in patients with advanced non-small cell lung cancer of different EGPR phenotypes. Clinical data of patients with advanced non-small cell lung cancer who received Icotinib treatment from August, 2011 to May, 2013 were retrospectively analyzed. Kaplan-Meier analysis was used for survival analysis and comparison. 18 wild-type EGFR and 51 mutant type were found in a total of 69 patients. Objective response rate of patients with mutant type EGFR was 54.9 % and disease control rate was 86.3 %. Objective response rate of wild-type patients was 11.1 % (P = 0.0013 vs mutant type), disease control rate was 50.0 % (P = 0.0017). Median progression-free survival (PFS) of mutant type and wild-type patients were 9.7 and 2.6 months, respectively (P Icotinib included rash, diarrhea, itching skin with occurrence rates of 24.6 % (17/69), 13.0 % (9/69), and 11.6 % (8/69), respectively. Most adverse reactions were grade I-II. Icotinib has great efficacy in EGFR mutated patients, making it an optimal regimen to treat EGFR mutated patients. Furthermore, most of adverse reactions associated with Icotinib treatment were tolerable.

  4. Chemotherapy related toxicity in locally advanced non-small cell lung cancer

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    Bahl Amit

    2006-01-01

    Full Text Available Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0 Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients. Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

  5. [Efficacy of MVP chemotherapy combined with concurrent radiotherapy for advanced non-small cell lung cancer].

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    Qiao, Tiankui; Zhou, Daoan; Chen, Wei; Wang, Xianglian

    2004-12-20

    To observe the effects of MVP chemotherapy combined with concurrent radiotherapy for stage IIIB-IV non-small cell lung cancer. Sixty-two patients with stage IIIB-IV non-small cell lung cancer were randomized into two groups, concurrent radiochemotherapy group and MVP che-motherapy group. All patients in two groups were treated with MVP regimen (mitomycin C 6 mg/m² on day 1, vindesine 2 mg/m² on days 1, 8, and cisplatin 80-100 mg/m²). Patients in concurrent radiochemotherapy group received concurrent radiotherapy (46-56 Gy in 5-6 weeks). All patients received 2-4 cycles of MVP chemotherapy. The response rate was 48.4% and 19.4% in concurrent radiochemotherapy group and MVP group respectively (P MVP group.. The results show that efficacy of MVP chemotherapy combined with concurrent radiotherapy is significantly higher than that of MVP chemotherapy alone for advanced non-small cell lung cancer.

  6. Advances in surgical techniques in non-small cell lung cancer.

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    Kim, Anthony W; Detterbeck, Frank C

    2013-12-01

    Thoracic surgery is a dynamic field, and many scientific, technological, technical, and organizational changes are occurring. A prominent example is the use of less invasive approaches to major resection of non-small cell lung cancer (NSCLC), both thoracoscopic and robotic. Sophisticated technology corroborated by clinical data has led to these approaches becoming accepted additions to the armamentarium. Additionally, improvements in perioperative pain management have also contributed to dramatically changing the experience of patients who undergo modern thoracic surgery. Lung cancer is being detected more often at an early stage. At the same time, advances in techniques, patient care, clinical science, and multidisciplinary treatment support an increased role for aggressive resection in the face of larger locally advanced tumors or for those with limited metastatic disease. These advances, conducted in the setting of multidisciplinary decision making, have resulted in real and palpable advancements for patients with lung cancer. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    Science.gov (United States)

    2017-04-12

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  8. CIMAvax-EGF®: Therapeutic Vaccine Against Non-small Cell Lung Cancer in Advanced Stages

    Directory of Open Access Journals (Sweden)

    Diana Rosa Fernández Ruiz

    2017-02-01

    Full Text Available Biotechnology is one of the scientific activities deployed by the Cuban State, which shows greater results and impact on the of the Cuban population health. It has increased the therapeutic repertoire in dealing with oncological diseases with products such as CIMAvax-EGF®, the first therapeutic vaccine of its kind, from the Molecular Immunology Center, against non-small cell lung cancer in advanced stages IIIB IV. The application of this product already extends to Primary Health Care with encouraging results, by prolonging the survival of patients with higher quality of life.

  9. Potential role of immunotherapy in advanced non-small-cell lung cancer

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    de Mello RA

    2016-12-01

    Full Text Available Ramon Andrade de Mello,1–3 Ana Flávia Veloso,4 Paulo Esrom Catarina,4 Sara Nadine,5 Georgios Antoniou6 1Department of Biomedical Sciences and Medicine, University of Algarve, Faro, 2Faculty of Medicine, University of Porto, Porto, Portugal; 3Research Center, Cearense School of Oncology, Instituto do Câncer do Ceará, 4Oncology & Hematology League, School of Medicine, State University of Ceará (UECE, Fortaleza, Brazil; 5Instituto de Ciências Biomédicas Abel Salazar (ICBAS, University of Porto, Porto, Portugal; 6Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, London, UK Abstract: Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib. As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework. Keywords: immunotherapy, non-small-cell lung cancer, nivolumab, pembrolizumab, ipilimumab, clinical trials, PD1, PDL1, CTLA4

  10. Present trends in the treatment of advanced non-small-cell lung cancer

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    Parvez, T.; Iskandrani, A.

    2003-01-01

    Lung cancer is the leading cause of cancer deaths all over the world. As most patients present with advanced disease, major efforts have been made in the treatment of such disease with systemic chemotherapy. Several new agents and new combinations of chemotherapy have been developed recently. This article reviews the randomized clinical trials investigating chemotherapy for advanced non-small cell lung cancer (NSCLC) in relapse or progressive disease while being treated and in elderly patients. Therapies that incorporate new biological agents to target specific defects in lung cancer are also discussed. Several clinical trials have demonstrated improvement in overall survival as well as quality of life with presently available chemotherapy treatment of advanced NSCLC. Better options are available for the elderly as well as those having relapse after first line chemotherapy. Despite all this progress the 5-year survival rate still remains at a dismal 14%. New therapies with good results are still desired. (author)

  11. Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer.

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    Ma, X-H; Tian, T-D; Liu, H-M; Li, Q-J; Gao, Q-L; Li, L; Shi, B

    2017-01-01

    To evaluate the efficacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and discuss the influence factors on efficacy. 120 treatment-experienced patients confirmed by pathology or cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib orally until the occurrence of disease progression or serious adverse reactions. Then, the efficacy of icotinib hydrochloride and the related influence factors were analyzed. In icotinib hydrochloride group, the response rate and the disease control rate were 30.00% and 65.00%, and the median progression-free survival time was 179 days (95% CI: 103.21-254.78); in erlotinib group, the response rate and the disease control rate were 25.00% and 56.70%, and the median progression-free survival time was 121 days (95% CI: 95.05-146.94). Moreover, the objective response rate and the disease control rate of second-line therapy were both superior to the third-line and above therapy. The objective response rate of patients with complete response/partial response/stable disease after the first-line therapy was higher than that of patients without response after the first-line therapy (picotinib hydrochloride is effective and safe in treating the treatment-experienced patients with advanced NSCLC, especially for patients with sensitive mutations.

  12. Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.

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    Gu, Aiqin; Shi, Chunlei; Xiong, Liwen; Chu, Tianqing; Pei, Jun; Han, Baohui

    2013-02-01

    To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (Picotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

  13. Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

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    Liang, Jun-Li; Ren, Xiao-Cang; Lin, Qiang

    2014-01-01

    Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC) patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. PMID:24876785

  14. Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer

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    Kim, Myung Soo; Lee, Ji Hae; Ha, Bo Ram; Lee, Re Na

    2011-01-01

    Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients. The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently. Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ≥2 radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ≥2 radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), V20, V30, V40, MLDipsi, V20ipsi, V30ipsi, and V40ipsi were associated with grade ≥2 radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ≥2 radiation pneumonitis. Concurrent

  15. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Nygaard, Anneli Dowler; Garm Spindler, Karen-Lise; Pallisgaard, Niels

    2013-01-01

    BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cf......DNA) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible....... RESULTS: The study included 246 patients receiving a minimum of 1 treatment cycle, and all but four were evaluable for response according to RECIST. Forty-three patients (17.5%) presented with a KRAS mutation. OS was 8.9 months and PFS by intention to treat 5.4 months. Patients with a detectable plasma...

  16. [Prognostic factors of advanced stage non-small-cell lung cancer].

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    Kwas, H; Guermazi, E; Khattab, A; Hrizi, C; Zendah, I; Ghédira, H

    2017-09-01

    Primary lung cancer is the leading cause of cancer death in men in the world. Although the introduction of new drugs, new therapeutic strategies and despite therapeutic advances, the prognosis is relatively improved during the last years. To evaluate the prognosis of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors at these stages. A retrospective study, including 140 cases of locally advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013. The average age was 61±10 years (35 to 90 years). Sex ratio was 18. The delays management were 80±25 days for presentation, 45±20 days for the diagnostic, while the treatment delay was 8±2.33 days. The cancer was at stage IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was between 50 and 74% and between 9 and 25%, respectively. Better survival was observed in patients with NSCLC on stage III, having better performance status, having comorbid conditions, with prolonged delays management, a short therapeutic delay and patients who received specific antitumor treatment. The prognostic factors in locally advanced and metastatic NSCLC in our patients were: stage of cancer, performance status, comorbid conditions, delay of management and specific antitumoral treatment. These factors should be considered in the management of patients with advanced NSCLC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Improved radiotherapy for locally advanced Non-Small Cell Lung Carcinoma (NSCLC) patients

    DEFF Research Database (Denmark)

    Ottosson, Wiviann

    to comply with the DIBH technique. For DIBH, the patients are guided to hold their breath almost at their maximum inspiration level during imaging and treatment. This leads to reduction of the breathing motion which decreases the movement of the tumor and OARs. It also expands the lung tissue which...... be reduced by the DIBH method for the lung cancer patients. The overall aim of the clinical part of this thesis was to clarify the potential benefit of offering DIBH gating, compared to free-breathing (FB), for lung cancer patients. Particularly, the benefits for locally advanced non-small cell lung cancer...... (NSCLC) patients were explored. For the dosimetric part of the thesis, the dosimetric aspects of correct dose calculations in heterogeneous patient-like geometries were studied. The clinical aspects of DIBH were evaluated in three different studies, where planning and setup verification images acquired...

  18. Improving chemotherapy for patients with advanced non-small cell lung cancer

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    von Plessen, Christian

    2011-01-01

    INTRODUCTION: Lung cancer is the third most common mortal disease in industrialised countries and the prognosis has been slow to improve. The largest subgroup has locally advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, these patients can usually not be cured and the main...... project. The description of the experiences can serve as an example for the improvement of microsystems in settings with similar problems. Finally, in the registry study of Norwegian patients with lung cancer, we found significant geographical and temporal variations of the utilisation of chemotherapy...... that were related to survival. Potential areas of improvement in the system of care for lung cancer are recruitment of patients in clinical studies, standardisation of the processes of care in outpatient clinics, definition of strategic aims of quality, development of balanced quality indicators, as well...

  19. Serum peptide expression and treatment responses in patients with advanced non-small-cell lung cancer

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    An, Juan; Tang, Chuan-Hao; Wang, Na; Liu, Yi; Lv, Jin; Xu, Bin; Li, Xiao-Yan; Guo, Wan-Feng; Gao, Hong-Jun; He, Kun; Liu, Xiao-Qing

    2018-01-01

    Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non-small-cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI-TOF MS was used on pretreatment serum samples of patients with advanced non-small-cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR-TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI-TOF MS analysis can be used to predict responses to EGFR-TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation. PMID:29844828

  20. Gefitinib in advanced non-small cell lung cancer: does it deserve a second chance?

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    Stinchcombe, Thomas E; Socinski, Mark A

    2008-09-01

    There has been intense investigation into the epidermal growth factor receptor (EGFR) as a therapeutic target in the treatment of non-small cell lung cancer (NSCLC). Currently there are two EGFR tyrosine kinase inhibitors, erlotinib and gefitinib, approved for the treatment of advanced NSCLC. In a phase III trial (BR.21), treatment with erlotinib resulted in a statistically significant improvement in overall survival in patients who had experienced progression after one or two previous chemotherapy treatments in comparison with best supportive care (BSC). In contrast, in the Iressa Survival Evaluation in Lung Cancer (ISEL) trial, treatment with gefitinib did not result in a statistically significant improvement in overall survival time in comparison with BSC in patients who had received one or two previous chemotherapy treatments and were refractory to or intolerant of the previous chemotherapy. After the results of the ISEL trial, the U.S. Food and Drug Administration restricted the use of gefitinib, and gefitinib was effectively removed from routine clinical practice within the U.S. However, gefitinib was approved in other countries and clinical trials investigating gefitinib continued. Recently the Iressa Non-small cell lung cancer Trial Evaluating REsponse and Survival against Taxotere (INTEREST) trial met the primary endpoint of demonstrating noninferiority in terms of overall survival for gefitinib (250 mg daily) in comparison with docetaxel (75 mg/m(2) every 3 weeks). Patients treated with gefitinib experienced a lower rate of treatment-related toxicity and higher rate of improvement in quality of life. Results of recent gefitinib trials have been provocative, and suggest a role for gefitinib in the treatment of advanced NSCLC.

  1. Chemotherapy options for the elderly patient with advanced non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Hennessy, B T

    2012-02-03

    Combination chemotherapy has been shown to improve overall survival compared with best supportive care in patients with advanced non-small cell lung cancer (NSCLC). The survival advantage is modest and was initially demonstrated with cisplatin-containing regimens in a large meta-analysis of randomized trials reported in 1995. Newer chemotherapy combinations have been shown to be better tolerated than older cisplatin-based combinations, and some trials have also shown greater efficacy and survival benefits with these newer combinations. Combination chemotherapy is, therefore, the currently accepted standard of care for patients with good performance statuses aged less than 70 years with advanced NSCLC. However, there are limited data from clinical trials to support the use of combination chemotherapy in elderly patients over 70 years of age with advanced NSCLC. Subgroup analyses of large randomized phase III trials suggest that elderly patients with good performance statuses do as well as younger patients treated with combination chemotherapy. There are few randomized trials reported that evaluate chemotherapy in patients aged greater than 70 years only. Based on data from trials performed by an Italian group, single-agent vinorelbine has been shown to have significant activity in elderly patients with advanced NSCLC and to be well tolerated by those patients with Eastern Cooperative Oncology Group performance statuses of two or less, with associated improvements in measures of global health.

  2. [Comparison of NP and MVP regimen in treatment of advanced non-small cell lung cancer].

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    Qiang, E; Wang, Song-ping; Liu, Shu-juan; Yiao, Juan

    2002-12-01

    Chemotherapy is the major treatment for advanced non-small cell lung cancer (NSCLC). However, the efficacy is not satisfactory. From January 1996 to December 2000, two chemotherapy regimen [NP: vinorelbine(NVB) + cisplatin(DDP); MVP: mitomycin (MMC) + vindesine(VDS) + cisplatin] have been used to treat 110 advanced NSCLC patients. The response and major adverse reaction were analyzed and compared. Forty-eight cases of advanced NSCLC (stage III-IV) patients were treated with NP (NVB: 25 mg/m2, d1, 8; DDP: 35 mg/m2, d1-3). The other 62 cases were treated with MVP regimen (MMC: 6 mg/m2, d1; VDS: 3 mg/m2, d1, 8; DDP: 30 mg/m2 d1-3). In NP group, the overall response rate was 50% (CR + PR = 24); medium response time was 5.5 months; medium survival time was 11 months. In MVP group, the overall response rate was 51.6% (CR + PR = 32), medium response time and survival time were 6.5 and 14.5 months, respectively. The major toxicities were myelosuppression and phlebitis in NP group, nausea/vomiting, myelosuppression in MVP group, respectively. NP and MVP regimen for advanced NSCLC have similar response rate (P > 0.05). Deep vein injection and improved infusion can be used to prevent phlebitis in NP regimen.

  3. Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Cho, Kwan Ho

    2004-01-01

    Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

  4. Efficacy of Icotinib Hydrochloride in the Treatment of Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xianglei Ma

    2013-09-01

    Full Text Available Objective: To observe and evaluate the efficacy and adverse responses of icotinib hydrochloride in the treatment of advanced non-small cell lung cancer (NSCLC, and analyze the relative factors impacting its efficacy and prognosis. Methods: The clinical data of 260 patients with advanced NSCLC treated with icotinib hydrochloride in Jiangsu Cancer Hospital was retrospectively analyzed. Results: Four weeks after initial administration, 256 patients were evaluable for efficacy except 4 who withdrew the drug due to intolerable adverse responses. Among the 256 patients, there were 0 complete response (CR, 96 partial response (PR, 37.5%, 97 stable disease (SD, 37.9% and 63 progression disease (PD, 24.6%, with the objective remission rate (ORR and disease control rate (DCR being 37.6% and 75.4% respectively. However, in all patients, the median progression-free survival (PFS was 7 (0.4 - 16.3 months, and were 11 (1 - 16.3, 6 (0.4 - 11.3 and 5 (1 - 13.5 months in those treated with first-line, second-line, and ≥third-line treatments, respectively. Conclusion: Icotinib hydrochloride has significant efficiency and better safety for treating advanced NSCLC.

  5. The End of Nihilism: Systemic Therapy of Advanced Non-Small Cell Lung Cancer.

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    Ernani, Vinicius; Steuer, Conor E; Jahanzeb, Mohammad

    2017-01-14

    Lung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non-small cell lung cancer (NSCLC) comprises 85-90% of lung cancers. Historically, the expected survival of patients with advanced disease has been estimated in months. In recent years, however, lung cancer has come to be seen as a treatable disease with multiple therapeutic options. Enormous advances in the understanding of its pathways and mechanisms have enabled personalized therapy in NSCLC. The evolving approach to therapy focuses on genomic profiling of the tumors to find molecular targets and develop specific agents for individualized therapy. In addition, maintenance therapy has emerged as a valid approach, and the choice of chemotherapy now varies by histology. Most recently, immunotherapy with checkpoint inhibitors has shown promising results, with impressive durations of response and a tolerable toxicity profile. Together, these discoveries have improved overall survival substantially in patient populations that have access to these advancements. We review the clinical data surrounding these impressive improvements.

  6. Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab.

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    Stinchcombe, Thomas E

    2007-09-01

    Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting.

  7. Supportive care in the era of immunotherapies for advanced non-small-cell lung cancer.

    Science.gov (United States)

    Awada, Gil; Klastersky, Jean

    2018-03-01

    The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting. These immunotherapies are associated with a distinct toxicity profile based on autoimmune organ toxicity which is a new challenge for supportive care during treatment with these drugs. The differential diagnosis of events occurring during immune checkpoint inhibitor treatment is broad: they can be due to immune-related or nonimmune-related adverse events, atypical tumor responses (pseudoprogression or hyperprogression) or events related to comorbidities or other treatments. The management of these patients includes a thorough baseline clinical, biological and radiologic evaluation, patient education, correct follow-up and management by a multidisciplinary team with a central role for the medical oncologist. Immune-related toxicities should be managed according to available guidelines.

  8. Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

    Directory of Open Access Journals (Sweden)

    Liang JL

    2014-05-01

    Full Text Available Jun-Li Liang,1 Xiao-Cang Ren,2 Qiang Lin2 1Department of Radiation Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, People’s Republic of China; 2Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, Renqiu, Hebei Province, People’s Republic of China Abstract: Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. Keywords: targeted therapy, EGFR-TKI, NSCLC

  9. [Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

    Science.gov (United States)

    Li, Xi; Yang, Xin-jie; Sun, Yi-fen; Qin, Na; Lü, Jia-lin; Wu, Yu-hua; Zhang, Hui; Zhang, Quan; Zhang, Shu-cai

    2012-08-01

    To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

  10. [Efficacy of icotinib for advanced non-small cell lung cancer patients with EGFR status identified].

    Science.gov (United States)

    Song, Zhengbo; Yu, Xinmin; Cai, Jufen; Shao, Lan; Lin, Baochai; He, Chunxiao; Zhang, Beibei; Zhang, Yiping

    2013-03-01

    As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (Picotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity. Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

  11. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Minami S

    2015-01-01

    Full Text Available Seigo Minami,1 Takashi Kijima2 1Department of Respiratory Medicine, Osaka Police Hospital, 2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan Abstract: Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC. Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be

  12. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    Science.gov (United States)

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  13. Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Meina WU

    2011-03-01

    Full Text Available Background and objective As there is a sharp increase in the incidence of lung cancer in women in recent years, it has brought broad concerns with its unique clinical and epidemiological characteristics and better prognosis. The aim of this study is to analyze the clinical data of women with advanced non-small cell lung cancer (NSCLC retrospectively to explore the prognostic factors. Methods Clinical data of 541 female patients with advanced NSCLC were collected and followed up till death. The primary endpoint is overall survival (OS. SPSS 11.0 statistical analysis software was used for univariate and multivariate analysis. Results The mean age is 59 years (20 years-86 years, adenocarcinoma account for 80.2% (434/541. The median OS was 15 months (95%CI: 13.87-16.13, and 1, 2, 5-year survival rates were 58.8%, 23.7% and 3.20% respectively. Univariate analysis showed that clinical stage, ECOG score, weight loss, clinical symptoms, liver/bone/brain metastasis and received more than one chemotherapy regimen, good response to the first-line chemotherapy, EGFR-TKI targeted therapy and radiotherapy treatment were significantly correlated with the OS and survival rate (P < 0.05. Combined with multivariate analysis, weight loss before treatment, ECOG score, received EGFR-TKI targeted therapy and response to first-line chemotherapy were independent prognostic factor for survival (P < 0.05. Conclusion There is a higher percentage of adenocarcinoma in female NSCLC. Weight loss before treatment, ECOG score, EGFR-TKI targeted therapy and response to first-line chemotherapy may become independent prognostic factors for survival of female patients with advanced NSCLC.

  14. Palliative radiotherapy in asymptomatic patients with locally advanced, unresectable, non-small cell lung cancer

    International Nuclear Information System (INIS)

    Reinfuss, M.; Skolyszewski, J.; Kowalska, T.; Rzepecki, W.; Kociolek, D.

    1993-01-01

    Between 1983 and 1990, 332 patients with non-small cell lung cancer (NSCLC) were referred to short-time, split-course palliative thoracic radiotherapy. The group consisted of patients with locally advanced (III o ), unresectable cancer, not suitable for curative radiotherapy, asymptomatic or having only minimal symptoms related to intrathoracic tumor. The therapeutic plan involved two series of irradiation. Tumor dose delivered in each series was 20 Gy given in five daily fractions over five treatment days. There were four weeks interval between series. Of 332 patients initially qualified to thoracic radiotherapy only 170 patients received the treatment; the other 162 patients were not irradiated because of treatment refusal or logistic problems concerning therapy. They made the control group of the study, receiving the best possible symptomatic care. Twelve-month survivals in the radiotherapy and control groups were 32.4% and 9.3%, respectively; 24-month survivals 11.2% and 0%, respectively. Improvement of survival after palliative thoracic radiotherapy was observed only in patients with clinical stage IIIA and Karnofsky's performance status (KPS) ≥ 70. (orig.) [de

  15. Exploring hope and healing in patients living with advanced non-small cell lung cancer.

    Science.gov (United States)

    Eustache, Chloe; Jibb, Emily; Grossman, Mary

    2014-09-01

    To explore the experience and meaning of hope in relation to the healing process of patients living with stage IIIb or IV non-small cell lung cancer. Interpretative qualitative study design. Peter Brojde Lung Cancer Centre in the Jewish General Hospital in Montreal, Quebec, Canada. 12 English- and French-speaking patients, aged 36-78 years. One 60-90-minute semistructured interview per participant was conducted. An inductive approach to data analysis was taken, involving immersion in the data, coding, classifying, and creating linkages. Four main themes emerged: (a) the morass of shattered hope, (b) tentative steps toward a new hope paradigm, (c) reframing hope within the context of a life-threatening illness, and (d) strengthening the link between hope and wellness. Patients described a process where hope was diminished or lost entirely, regained, and reshaped as they learned to live and grow following their diagnosis. This study adds to the literature by describing the dynamic nature of hope as well as factors facilitating or hindering the hope process. It demonstrates how finding meaning, a structural component of healing, can be used to envision a new hopeful future. This study suggests hope and healing cannot exist in isolation, and highlights the importance of understanding the fluctuating nature of hope in patients with advanced lung cancer to foster it, therefore promoting healing.

  16. Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

    Science.gov (United States)

    Bianco, A; Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Rodriguez, R; Cuevas, M A; Alvarez, L A

    1990-02-28

    Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

  17. Combined modality therapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Recine, D.; Rowland, K.; Reddy, S.; Lee, M.S.; Bonomi, P.; Taylor, S.; Faber, L.P.; Warren, W.; Kittle, C.F.; Hendrickson, F.R.

    1990-01-01

    Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting

  18. Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Pérez, Juan E; Machiavelli, Mario R; Romero, Alberto O; Romero Acuña, Luis A; Domínguez, María E; Fasce, Hebe; Flores Acosta, Luis; Marrone, Nora; Romero Acuña, Juan M; Langhi, Mario J; Amato, Sonia; Bologna, Fabrina; Ortiz, Eduardo H; Leone, Bernardo A; Lacava, Juan A; Vallejo, Carlos T

    2002-08-01

    A phase II trial was performed to evaluate the efficacy and toxicity of the novel combination of vinorelbine and paclitaxel as first-line chemotherapy in patients with stages IIIB and IV non-small-cell lung cancer. From January 1997 to September 1999, 34 patients (9 stage IIIB and 25 stage IV) received a regimen consisting of the following: vinorelbine 30 mg/m2 20 minutes intravenous (i.v.) infusion, days 1 and 8; and paclitaxel 135 mg/m2 3-hour i.v. (starting 1 hour after vinorelbine) on day 1. Cycles were repeated every 28 days until progression of disease or unacceptable toxicity development. The median age was 57 years (range 41-70 years); median performance status was 1. Histology was as follows: squamous cell in 24 (71%), large cell in 1 (3%), and adenocarcinoma in 9 (26%). All patients are evaluable for toxicity, whereas 30 are evaluable for response (4 patients refused treatment). Objective response was recorded in 4 of 30 patients (13%, 95% CI 1-25%). No complete response was observed. Partial response was recorded in 4 patients (13%), no change in 10 patients (34%), and progressive disease in 16 patients (53%). The median time to treatment failure was 4 months and median survival was 9 months. The limiting toxicity was myelosuppression: leukopenia in 23 patients (68%), whereas neutropenia was observed in 25 patients (78%). Peripheral neurotoxicity developed in 14 patients (41%) (without G3 or G4 episodes), and constipation (G1-G2: 10 patients), myalgia (G1-G2: 11 patients), diarrhea (G1-G2: 7 patients), and stomatitis were observed in 7 patients. Vinorelbine-paclitaxel combination showed only modest activity against locoregionally advanced or metastatic NSCLC.

  19. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer.

    Science.gov (United States)

    Minami, Seigo; Kijima, Takashi

    2015-01-01

    Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR) mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be a pivotal drug when a combination maintenance therapy is used in practice. For future maintenance therapy, we need to explore reliable predictive selection or exclusion markers that can predict who will really benefit from maintenance therapy.

  20. Recent advances in the treatment of non-small cell and small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2014-01-01

    Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR tyrosine kinase inhibitors. However, inevitably, patients experience disease progression and the most common mechanism of acquired resistance is an EGFR exon 20 T790M mutation. Several agents (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients with T790M resistance mutations. Additional data on the efficacy of first-line therapy with afatinib and the combination of erlotinib and bevacizumab for patients with EGFR mutant NSCLC were presented. The results of a phase III trial of crizotinib compared to platinum-pemetrexed in the first-line setting, and a phase I trial and expansion cohort of ceritinib, provided additional efficacy and toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A phase III trial of cisplatin and gemcitabine, with and without necitumumab, revealed an improvement in overall survival with the addition of necitumumab in patients with squamous NSCLC. In the second-line setting, a phase III trial of docetaxel with ramucirumab or placebo revealed an improvement in overall survival with the addition of ramucirumab. In extensive stage small cell lung cancer phase III trials of consolidative thoracic radiation therapy and prophylactic cranial radiation failed to reveal an improvement in overall survival.

  1. Efficacy of Icotinib for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified

    Directory of Open Access Journals (Sweden)

    Yiping ZHANG

    2013-03-01

    Full Text Available Background and objective As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Methods Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. Results The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation with NSCLC were enrolled in the current study. The patients’ overall objective response rate (ORR was 58.3% and the disease control rate (DCR in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001. Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41. Median overall survival (OS in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II and reversible with no grade IV toxicity. Conclusion Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

  2. Current treatments for advanced stage non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A

    2009-04-15

    Lung cancer remains the leading cause of cancer mortality in the United States, and the majority of patients will have non-small cell lung cancer (NSCLC) and will present with locally advanced or metastatic disease. In the United States, the most common histology is adenocarcinoma, followed by squamous cell, large cell, and not otherwise specified. For patients with a preserved performance status (PS), double agent platinum-based therapy extends survival, improves quality of life (Qol), and reduces disease-related symptoms. The addition of a third cytotoxic agent increases toxicity without any clinical benefit. However, the addition of a targeted agent (bevacizumab, an antiangioegenesis agent, or cetuximab, an antibody against the epidermal growth factor receptor [EGFR]) to platinum-based therapy has yielded an improvement in survival compared with platinum-based therapy alone. To receive bevacizumab, patients are required to have nonsquamous histology, a PS of 0 or 1, and no evidence of brain metastases, hemoptysis, uncontrolled hypertension, and no need for therapeutic anticoagulation. The benefits of chemotherapy for patients with a poor performance status are less well defined, and the current recommendations are for treatment with single-agent chemotherapy. Elderly patients (defined as age > or = 70 yr) derive a survival and Qol benefit from chemotherapy treatment, and for the majority of elderly patients single-agent chemotherapy is the standard. However, elderly patients with a good performance status and without co-morbidities can tolerate platinum-based therapy without excessive toxicity and appear to derive a survival benefit similar to that in younger patients. Recently, a separate population of patients defined by a light or never-smoking history has been identified. This patient population appears to have unique clinical and molecular characteristics, and may benefit from initial therapy with an EGFR tyrosine kinase inhibitor. Once patients have

  3. Concurrent versus Sequential Chemoradiotherapy with Cisplatin and Vinorelbine in Locally Advanced Non-Small Cell Lung Cancer: A Randomized Study

    Czech Academy of Sciences Publication Activity Database

    Zatloukal, P.; Petruželka, L.; Zemanová, M.; Havel, L.; Janků, F.; Judas, L.; Kubík, A.; Křepela, E.; Fiala, P.; Pecen, Ladislav

    2004-01-01

    Roč. 46, - (2004), s. 87-98 ISSN 0169-5002 Institutional research plan: CEZ:AV0Z1030915 Keywords : concurrent chemoradiotherapy * sequential chemoradiotherapy * locally advanced non-small cell lung cancer * cisplatin * vinorelbine Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.914, year: 2004

  4. Kanglaite for Treating Advanced Non-small-cell Lung Cancer: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Lina ZHU

    2009-03-01

    Full Text Available Background and objective In the past years, many reports on Kanglaite were publicated in China, researchers across the country. The aim of this study is to review the effectiveness and safety of Kanglaite for treating advanced non-small-cell lung cancer. Methods Authors searched the Cochrane Library, Pubmed, Embase, Cancerlit,CBM, CNKI and VIP. Mannual and additional search were also conducted. All randomized controlled trials/quasi- RCT comparing Kanglaite with other lung cancer treatment were included. Two reviewers independently performed data extraction and appraised the publications using the Juni instrument, disagreements were resolved by consensus. Double data were entered and analyzed by RevMan 4.2 software are by Cochrane Collaboration. Results Sixteen reports wereincluded in the meta-analysis. The quality of 16 studies was low. Pooling data of 5 studies indicated that the effect of Kanglaite+NP (Vinorelbine+Cisplatin was better than NP with RR 1.46, 95% Confidence Interval 1.13 to 1.91. Pooling data of 3 studies of MVP (Mitomycin+Vindsine+ Cisplatin plus Kanglaite indicated that the effect was better with RR 1.84, 95%CI 1.22 to 2.76. Pooling data of 2 studies showed that the effect of GP (Gemcitabine+Cisplatin plus Kanglaite was better than GP with RR 1.63, 95%CI 1.09 to 2.43. Fourteen studies revealed that Kanglaite may reduce the side-effectinduced by regular treatment. Ten studies showed regular treatment plus Kanglaite can stabilite/improve quality of life. Conclusion Kanglaite can enhance clinical effect of regular treatment, reduce side-effect and stabilite/improve quality of life, but the effect of Kanglaite being used in clinical settings needs to be confirmed by further large and multicenter.

  5. Maintenance therapy in advanced non-small cell lung cancer: current status and future implications.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A

    2011-01-01

    Maintenance therapy for patients with advanced non-small cell lung cancer has been an area of intense investigation. Maintenance therapy has been divided into two broad categories: continuation maintenance when the chemotherapy or targeted agent was part of a defined number of cycles of combination therapy and in the absence of disease progression is continued as a single agent or switch maintenance when a third agent is initiated after four cycles of platinum-based double-agent chemotherapy in the absence of disease progression. Two monoclonal antibodies, cetuximab and bevacizumab, are used as continuation maintenance, but the incremental benefit of the maintenance therapy with these agents is undetermined. Phase III trials have not revealed an overall survival benefit for continuation maintenance chemotherapy, and this approach should be considered investigational. Phase III trials have demonstrated an improvement in overall survival with switch maintenance therapy with pemetrexed compared with placebo in patients with nonsquamous histology and erlotinib compared with placebo. Phase III trials have not revealed an improvement in quality of life with maintenance therapy. In the trials of maintenance therapy, 30 to 40% of patients enrolled in the observation or placebo arm did not receive second-line therapy, and among the patients who did receive second-line therapy, there was significant heterogeneity in the therapy. The development of maintenance therapy has raised issues about the role of treatment-free intervals in routine clinical care, trial design issues such as the optimal endpoint, the ethics of a placebo arm, and the implications of maintenance therapy for first-line trials.

  6. Advances of Drug Resistance Marker of Gemcitabine for Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Baorui LIU

    2011-05-01

    Full Text Available With the development of pharmacogenomics and pharmacogenetics, personal therapy based on genes has become one of the most effective ways to enhance chemotherapeutic effect on non-small cell lung cancer (NSCLC patients. Much attention has been paid to validate the predictive biomarkers of chemotherapy in order to guide chemotherapy and enhance effect in general. Gemcitabine is one of the common agents treating NSCLC recently. This review is mainly about the recent reports on potential biomarkers of Gemcitabine in tailored therapy of NSCLC.

  7. Gemcitabine, cisplatin, and hyperfractionated accelerated radiotherapy for locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Zwitter, Matjaz; Kovac, Viljem; Smrdel, Uros; Strojan, Primoz

    2006-09-01

    Due to potent radiosensitization and potential serious or fatal toxicity, concurrent gemcitabine and irradiation should only be applied within clinical trials. We here present experience from a phase I-II clinical trial for patients with locally advanced non-small cell lung cancer (NSCLC) treated with hyperfractionated accelerated radiotherapy and concurrent low-dose gemcitabine. Eligible patients had locally advanced inoperable NSCLC without pleural effusion, Eastern Cooperative Oncology Group performance status 0-1, were chemotherapy naïve and had no previous radiotherapy to the chest, and had adequate hematopoietic, liver, and kidney function. Routine brain computed tomography was not performed, and positron emission tomography/computed tomography was not available. Treatment consisted of three parts: induction chemotherapy with gemcitabine and cisplatin in standard doses, local treatment with concurrent chemotherapy and radiotherapy, and consolidation chemotherapy. Patients were irradiated with opposed AP-PA and oblique fields, using 2.5-D treatment planning. Although corrections for inhomogeneous tissue were made, volume of total lung receiving > or =20 Gy (V20) could not be determined. The trial started as phase I, aimed to determine the dose-limiting toxicity and maximal tolerated dose (MTD) for concurrent hyperfractionated radiotherapy (1.4 Gy twice daily) and gemcitabine 55 mg/m twice weekly as a radiosensitizer. Phase II of the trial then continued at the level of MTD. Twenty-eight patients with NSCLC, nine patients with stage IIIA, 16 patients with IIIB, and three patients with an inoperable recurrence after previous surgery, entered the trial. The first 12 patients entered Phase I of the trial at the initial level of 42 Gy in 30 fractions in 3 weeks. Dose-limiting toxicity was acute esophagitis; 47.6 Gy in 34 fractions in 3.5 weeks was the MTD for this regimen of concurrent chemotherapy and radiotherapy. In phase II of the trial, this dose was applied

  8. [Clinical effects for patients with recurrent advanced non-small cell lung cancer treated with icotinib hydrochloride].

    Science.gov (United States)

    Nong, Jingying; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Hui; Wu, Yuhua; Lv, Jialin; Zhang, Quan; Zhang, Shucai

    2013-05-01

    Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0%. The median progression-free survival (PFS) time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively). RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively). RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

  9. Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Dan PU

    2013-11-01

    Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

  10. The Impact of Smoking Status on the Efficacy of Erlotinib in Patients with Advanced Non-small Cell Lung Cancer

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    Yilong WU

    2009-12-01

    Full Text Available Background and objective Erlotinib is a targeted treatment for advanced non-small cell lung cancer. Smoking status may be one of influencing factors of the efficacy of erlotinib. The aim of this study is to explore the impact of smoking status on the efficacy of erlotinib in patients with advanced non-small cell lung cancer. Methods Patients with nonsmall cell lung cancer who had been previously treated with at least one course of platinum based chemotherapy received 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression-free survival, overall survival were analyzed in the different smoking status groups. Kaplan-Meier method was used to analyze the survival rate. Results Fortyeight patients were enrolled into the study from December 2005 to September 2006. We followed up these patients until 28th December, 2008. Median follow up time was 30 months. The compliance rate was 100%. The response rate was 32.1% in the smoking group and 35% in the never smoking group (P=0.836; The median progression-free survival was 3 months and 9 months, respectively (P=0.033. The median overall survival was 5 months and 17 months, respectively (P=0.162. Conclusion Erlotinib is an effective drug for advanced non-small cell lung cancer patients with different smoking status. Progressionfree survival is better in the never smoking patients than the smoking patients.

  11. A Meta-Analysis of Platinum Plus Gemcitabine or Vinorelbine for Advanced Non-small Cell Lung Cancer

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    Guanghui GAO

    2009-01-01

    Full Text Available Background and objective Platinum plus the third-generation agent doublet chemotherapy is the standard regimens and first line chemotherapy for advanced non-small cell lung cancer (NSCLC. The aim of this study is to determine the benefits and harms of platinum plus gemcitabine or vinorelbine for advanced NSCLC. Methods Thedatabases PubMed, CENTRAL, EMBASE and Chinese Biomedical Literature database were retrieved by using the key words "non small cell lung cancer" or "Carcinoma, Non Small Cell Lung" so as to search the studies about the randomized controlled clinical trials (RCT that had compared the gemcitabine plus platinum versus vinorelbine plus platinum for advanced NSCLC. A meta-analysis was conducted. Results Nine randomized controlled trials, with total 2 186 patients,were included. The overall response rate and one-year survival rate of the gemcitabine group were not significantly different from that of vinorelbine regimen (RR=0.91, 95%CI: 0.81-1.03, P =0.15; RR=1.06, 95%CI: 0.96-1.18, P =0.27, respectively. The incidence rate of grade 3-4 netropenia, constipation, phlebitis and grade 1-4 neuropathy were higher in vinorelbine group, just like higher incidence rate of grade 3-4 thrombocytopenia in the gemcitabine group. Conclusion The curative effects of the gemcitabine or vinorelbine plus platinum regimens are similar. The choice of gemcitabine or vinorelbine depends on the toxicity of the drugs and patients' tolerance.

  12. Chemotherapy for advanced non-small cell lung cancer in the elderly population

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    Fábio Nasser Santos

    Full Text Available ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs. As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10, MEDLINE (1966 to 31 October 2014, EMBASE (1974 to 31 October 2014, and Latin American Caribbean Health Sciences Literature (LILACS (1982 to 31 October 2014. In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS, one-year survival rate (1yOS, progression-free survival (PFS, objective response rate (ORR, major adverse events, and quality of life (QoL. MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy

  13. Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer.

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    Shepherd, F A; Evans, W K; Goss, P E; Latreille, J; Logan, D; Maroun, J; Stewart, D; Warner, E; Paul, K

    1992-02-01

    Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.

  14. Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.

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    Vallejo, C; Romero, A; Perez, J; Cuevas, M; Lacava, J; Sabatini, C; Dominguez, M; Rodriguez, R; Barbieri, M; Romero Acuña, L; Romero Acuña, J; Langhi, M; Amato, S; Salvadori, M; Ortiz, E; Machiavelli, M; Leone, B

    1996-12-01

    We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

  15. Clinical Effects for Patients with Recurrent Advanced Non-small Cell Lung Cancer Treated with Icotinib Hydrochloride

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    Jingying NONG

    2013-05-01

    Full Text Available Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC. Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR was 45.0% and the disease control rate (DCR was 80.0%. The median progression-free survival (PFS time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively. RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively. RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively . There was no statistical difference in RR and PFS between those age <65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020. EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively. The side effects were generally mild and consisted of rash and diarrhea. Conclusion Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

  16. PD-L1 Expression and Survival among Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy

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    Sørensen, Steffen Filskov; Zhou, Wei; Dolled-Filhart, Marisa

    2016-01-01

    with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD......-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9...... by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy....

  17. The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

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    Rusch, V.W.; Griffin, B.R.; Livingston, R.B. (Univ. of Washington, Seattle (USA))

    1989-10-01

    Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

  18. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

  19. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Jakobsen, Kristine Raaby; Paulsen, Birgitte Sandfeld; Bæk, Rikke

    2015-01-01

    Background: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell...... control subjects based on the differential display of exosomal protein markers. Methods: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa–IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array...... (EV Array) was used to phenotype exosomes directly from the plasma samples. The array contained 37 antibodies targeting lung cancer-related proteins and was used to capture exosomes, which were visualised with a cocktail of biotin-conjugated CD9, CD63 and CD81 antibodies. Results: The EV Array...

  20. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

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    Noemí Reguart

    2010-06-01

    Full Text Available Noemí Reguart1, Andrés Felipe Cardona2, Rafael Rosell31Medical Oncology Service, ICMHO, Hospital Clinic Barcelona, Barcelona, Spain; 2Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, D.C., Colombia; 3Medical Oncology Service, Catalan Institute of Oncology, ICO, Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainAbstract: Erlotinib hydrochloride (Tarceva® is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR, with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents.Keywords: erlotinib, tyrosine kinase inhibitors, first line, maintenance, non-small-cell lung cancer

  1. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

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    Shu Yong-Qian

    2010-09-01

    Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

  2. Feasibility of stereotactic body radiotherapy for locally-advanced non-small cell lung cancer

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    Katrina Woodford

    2017-10-01

    Full Text Available SBRT was feasible for approximately half of the locally-advanced NSCLC patients we assessed and for these patients has the potential to reduce a 30 fraction course to 12 fractions. Using SBRT in this setting requires compromises in techniques and further compromises may allow SBRT in a greater proportion of patients.

  3. Liquid fiducial marker performance during radiotherapy of locally advanced non small cell lung cancer

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    Rydhög, Jonas Scherman; Mortensen, Steen Riisgaard; Larsen, Klaus Richter

    2016-01-01

    We analysed the positional and structural stability of a long-term biodegradable liquid fiducial marker (BioXmark) for radiotherapy in patients with locally advanced lung cancer. Markers were injected via endoscopic- or endobronchial ultrasound in lymph nodes and reachable primary tumours. Marker...

  4. Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy

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    Pan, Yi; Brink, Carsten; Knap, Marianne

    2016-01-01

    PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...... significantly associated with esophagitis. The two models using the relative esophagus volume irradiated above 40Gy (V40, OR=2.18/10% volume) or the length of esophagus irradiated above 40Gy (L40, OR=4.03/5cm) were optimal. The upper part of esophagus was more sensitive and females experienced more toxicity...... than men. CONCLUSION: V40 and L40 were most effective dosimetric predictors of grade ⩾2 esophagitis. The upper part of esophagus was more sensitive....

  5. [Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified].

    Science.gov (United States)

    Li, Xi; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Xinyong; Lv, Jialin; Wu, Yuhua; Zhang, Hui; Nong, Jingying; Zhang, Quan; Zhang, Shucai

    2015-12-01

    Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation and wild-type. Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. The patients' overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6%) and diarrhea (16.1%). Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.


  6. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2-11.8 months), and median overall survival was 21.0 months (95% CI: 20.1-21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation.

  7. Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified

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    Xi LI

    2015-12-01

    Full Text Available Background and objective Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC patients with EGFR mutation and wild-type. Methods Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. Results The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type with advanced NSCLC were enrolled in this study. The patients’ overall objective response rate (ORR was 51.6 % and the disease control rate (DCR was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6% and diarrhea (16.1%. Conclusion Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.

  8. Retrospective analysis of third-line chemotherapy in advanced non-small cell lung cancer

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    Ali Murat Tatli

    2015-01-01

    Results: A total of 72 patients who had received third-line or higher chemotherapy were included in the analysis. The median age of patients was 49 years (range 41-76, and there were 13 (18.1% women and 59 (81.9% men. Estimated median survival was 26 months. Moreover, overall survival was significantly longer in patients for whom disease control was achieved after second-line chemotherapy compared to those with disease progression (34 vs. 17 months, respectively. Survival after third-line treatment was significantly longer in the group with Eastern Cooperative Oncology Group (ECOG performance status 0-1 at the beginning of third-line therapy compared to patients with a status of 2-3. Conclusions: In patients with advanced stage NSCLC, administration of third-line and higher systemic chemotherapy may be associated with increase in overall survival. Furthermore, greater increases in overall survival were also observed in patients for whom disease control was achieved after second-line therapy and in those with ECOG performance status of 0-1 before third-line treatment.

  9. Novel agents in development for advanced non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2014-09-01

    The identification of EGFR mutations and ALK rearrangements in nonsmall cell lung cancer (NSCLC) has led to the rapid development of targeted therapies and significant changes in the treatment paradigm. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and crizotinib are now standard therapies for patients with the appropriate molecular alteration. Current investigations are determining the mechanisms of resistance to targeted therapies and developing novel agents to combat resistance. For patients with KRAS mutant NSCLC, a phase III trial of the MEK inhibitor, selumetinib, has been initiated. For patients without a defined mutation or a mutation without a known targeted therapy, immunotherapy, ganetespib, nintedanib and MET inhibitors in combination with EGFR TKIs are in development. Preliminary results of phase III trials raise doubts about the future development of dacomitinib as a second-line agent.

  10. Expression of CD147 in advanced non-small cell lung cancer correlated with cisplatin-based chemotherapy resistance.

    Science.gov (United States)

    Zeng, H Z; Qu, Y Q; Liang, A B; Deng, A M; Zhang, W J; Xiu, B; Wang, H; Wang, H

    2011-01-01

    CD147, a widely expressed cell surface glycoprotein in cancer, is associated with tumor invasiveness and chemotherapy resistance. Recently, CD147 is also regarded as a potential therapeutic target for cancer therapy. The aim of the study was to investigate CD147 expression in non-small cell lung cancer (NSCLC), and evaluate its correlation with cisplatin-based chemotherapy resistance. In this study, we examined immunohistochemically the expression of CD147 in 118 advanced NSCLC cases treated with cisplatin-based chemotherapy, and then the association of CD147 expression with clinicopathological characteristics was analyzed. Furthermore, RNA interference approach was used to silence CD147 expression in a cisplatin-resistant human lung cancer cell line A549/DDP, and the inhibition effect of cisplatin on tumor cells was assayed by MTT. In the overall series, positive CD147 expression was observed in 101/118 (85.6%) cases. A membranous CD147 pattern was identified in 76/101 (75.2%) of CD147 positive tumors. CD147 membranous expression,but not the overall CD147 expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced NSCLC patients. In vitro results showed that silencing CD147 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, our study indicated that membranous CD147 expression is a predictive factor of the response to cisplatin-based chemotherapies, and the use of CD147-targeted therapeutic adjuvants might be considered in the treatment of advanced NSCLC patients.

  11. Combination of docetaxel and cisplatin in the interventional treatment of advanced non-small cell lung cancer

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    He Zhijiang; Liu Yunjun; Li Ezhen

    2004-01-01

    Objective: To evaluate the efficacy and toxicity of the combination of docetaxel and cisplatin in the interventional treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods: Thirty patients with locally advanced (stage III) or metastatic (stage IV) NSCLC were enrolled into the study. The patients received docetaxel 75 mg/m 2 per day by bronchial artery and vein, and cisplatin 40 mg 2 on day 1-3 of a 21-day cycle. Each patient should complete two cycles. Results: An objective response rate was obtained in 46.7% of 30 patients (one complete and 13 partial response), whereas 10 patients had stable disease and 6 patients were progressive. The response rate was 60% (9/15) in the initial patients, and 33.3% (5/15) in the retreated patients. The main toxicities were leukopenia (26.7% in grade III + IV) and thrombocytopenia (10% in grade III + IV). Conclusion: The combination of docetaxel and cisplatin by interventional treatment is a feasible, well-tolerated and active scheme in the treatment of advanced NSCLC. (authors)

  12. Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer

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    Uğur Selek

    2014-12-01

    Full Text Available Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC. Three-dimensional radiotherapy (3DCRT has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT. IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques, treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.

  13. The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

    2015-05-10

    Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (PGPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were 0.67 (P GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated with CYFRA21-1, CEA and TPS in patients with advanced NSCLC. However, GPS was more efficient in predicting prognosis of advanced NSCLC than these three single prognosis related tumor markers.

  14. Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

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    Xu J

    2017-10-01

    Full Text Available Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China Background: Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR-mutant non-small cell lung cancer (NSCLC who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure.Patients and methods: This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally. Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal.Results: Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS was 5.33 months (95% CI, 3.63–7.03 months. Moreover, the objective response rate (ORR was 11.1%, and the disease control rate (DCR was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4% and fatigue (37.0%.Conclusion: Apatinib plus

  15. Does advanced lung inflammation index (ALI) have prognostic significance in metastatic non-small cell lung cancer?

    Science.gov (United States)

    Ozyurek, Berna Akinci; Ozdemirel, Tugce Sahin; Ozden, Sertac Buyukyaylaci; Erdoğan, Yurdanur; Ozmen, Ozlem; Kaplan, Bekir; Kaplan, Tugba

    2018-01-22

    Lung cancer is the most commonly diagnosed and death-related cancer type and is more frequent in males. Non-small-cell lung cancer (NSCLC) accounts for about 85% of all case. In this study, it was aimed to research the relationship between advanced lung inflammation index (ALI) and the primary mass maximum standardized uptake value (SUVmax) and C-reactive protein (CRP) at initial diagnosis and the prognostic value of ALI in determining the survival in metastatic NSCLC. A total of 112 patients diagnosed as stage 4 non-small-lung cancer in our hospital between January 2006 and December 2013 were included in this study. ALI was calculated as body mass index (BMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR). The patients were divided into two groups as ALI ALI ≥ 18 (low inflammation). The log-rank test and Cox proportional hazard model were used to identify predictors of mortality. Evaluation was made of 94 male and 18 female patients with a mean age of 59.7 ± 9.9 years. A statistically significant negative relationship was determined between ALI and CRP values (P ALI and SUVmax values (P = .436). The median survival time in patients with ALI ALI ≥ 18, it was 16 months (P = .095). ALI is an easily calculated indicator of inflammation in lung cancer patients. Values <18 can be considered to predict a poor prognosis. © 2018 John Wiley & Sons Ltd.

  16. ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Nestle, Ursula; De Ruysscher, Dirk; Ricardi, Umberto; Geets, Xavier; Belderbos, Jose; Pöttgen, Christoph; Dziadiuszko, Rafal; Peeters, Stephanie; Lievens, Yolande; Hurkmans, Coen; Slotman, Ben; Ramella, Sara; Faivre-Finn, Corinne; McDonald, Fiona; Manapov, Farkhad; Putora, Paul Martin; LePéchoux, Cécile; Van Houtte, Paul

    2018-04-01

    Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation

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    Xiaowen JIANG

    2016-04-01

    Full Text Available Background and objective Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC treatment. Epithelial growth factor receptor (EGFR tyrosine kinase inhibitor (TKI can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS≥6 months] and analysis of the related risk factors for prognosis. Methods From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. Results The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010, Prior chemotherapy (P=0.001, Eastern Cooperative Oncology Group (ECOG score (P=0.001 were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1% and diarrhea (27 cases, 11.7%. Conclusion Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line.

  18. [Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation].

    Science.gov (United States)

    Jiang, Xiaowen; Wang, Wenxian; Zhang, Yiping

    2016-04-20

    Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC) treatment. Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS)≥6 months] and analysis of the related risk factors for prognosis. From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010), Prior chemotherapy (P=0.001), Eastern Cooperative Oncology Group (ECOG) score (P=0.001) were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1%) and diarrhea (27 cases, 11.7%). Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line. 
.

  19. ERCC1 protein as a guide for individualized therapy of late-stage advanced non-small cell lung cancer.

    Science.gov (United States)

    Gao, Zhiqiang; Han, Baohui; Shen, Jie; Gu, Aiqin; Qi, Dajiang; Huang, Jinsu; Shi, Chunlei; Xiong, Liwen; Zhao, Yizhuo; Jiang, Liyan; Wang, Huimin; Chen, Yurong

    2011-09-01

    Excision repair cross-complementation group 1 (ERCC1) protein has been associated with cisplatin resistance. The objective of this study was to investigate the correlation between ERCC1 protein levels and the therapeutic effect of individualized therapy in advanced non-small cell lung cancer (NSCLC). A total of 190 advanced NSCLC patients were included in this study. Patients were randomized into either the individualized therapy group or the standard therapy group at a ratio of 2:1. Patients in the standard therapy group were treated with either gemcitabine plus cisplatin or vinorelbine plus cisplatin. The expression of ERCC1 protein in lung cancer tissues of patients from the individualized therapy group was detected with immunohistochemistry. Patients with low ERCC1 levels received either gemcitabine plus cisplatin or vinorelbine plus cisplatin, and patients with high levels received gemcitabine plus vinorelbine. The main outcome assessments were response rate (RR), overall survival (OS) and time to progression (TTP). Follow-up data were recorded until September 30, 2010. RR, 1-year survival rate and TTP were not statistically significant. The median survival time was 10.10 months in the standard therapy group (95% CI 8.48-11.92) and 13.59 months in the individualized therapy group (95% CI 11.86-14.74). The difference in median survival time was significantly different between these groups (P=0.036). The median survival time was longer in the individualized group compared to the standard therapy group. ERCC1 protein expression in advanced NSCLC patients, however, was not significantly correlated with RR, OS and TTP in the individualized therapy group. Therefore, this study suggests that ERCC1 protein levels should be assessed in combination with additional biomarkers to determine an optimal index for individualized therapy in advanced NSCLC patients.

  20. Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Ou Guangfei; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Feng Qinfu; Zhou Zongmei; Lv Jima; Liang Jun; Wang Mei; Yin Weibo

    2007-01-01

    Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

  1. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Rothschild SI

    2014-09-01

    Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

  2. Prognostic significance of tissue polypeptidespecific antigen (TPS) in patients with advanced non-small cell lung cancer

    NARCIS (Netherlands)

    A. van der Gaast (Ate); C.H.H. Schoenmakers (Christian); T.C. Kok (Tjebbe); B.G. Blijenberg (Bert); W.C.J. Hop (Wim); T.A.W. Splinter (Ted)

    1994-01-01

    textabstractIn this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate

  3. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Valente Nancy

    2005-02-01

    Full Text Available Abstract Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC-derived exosomes (DEX loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC. Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4 and IV (N = 9 NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8, flu like illness (N = 1, and peripheral arm pain (N = 1. The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors

  4. Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Blake, Mónika; Mata-Moya, María Dolores de la; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

    2014-01-01

    Background: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Results: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8–18.2), and the median overall survival was 26.9 months (95% CI, 15.3–38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). Conclusions: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings

  5. Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

    Science.gov (United States)

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2017-01-01

    Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

  6. [Prospective randomized study of HMVP, MVP, and HVP regimens in treatment of advanced non-small cell lung cancer].

    Science.gov (United States)

    Gao, Jian-Fei; Li, Chang-Sheng; Zhang, Bi-Cheng; Du, Guang-Zu; Zhang, Xin-Hua; Wang, Jun; Zhu, Yu-Ze; Ou, Wu-Ling; Yang, Bo

    2004-04-01

    Non-small cell lung cancer (NSCLC) is hyposensitive to the normal first and second-line chemotherapy regimens. Camptothecin derivative is becoming a hot point in the treatment of advanced NSCLC. The objective of this article was to evaluate the response, toxicity, and survival time of HMVP, MVP, and HVP regimens (detail in below) in the treatment of advanced NSCLC. A total of 134 cases with advanced NSCLC was randomized into three groups: HMVP group [46 patients, hydroxycamptothecin (HCPT) 12 mg/m(2) from d1 to d5, mitomycin C (MMC) 6 mg/m(2) d1, vindesine (VDS) 2.5-3 mg/m(2) d1 and d8, cisplatin (DDP) 50 mg/m(2) d2 and d3], MVP group (44 patients, MMC, VDS and DDP were the same as HMVP group) and HVP group (44 patients, HCPT, VDS, DDP were the same as HMVP group). The response rates were 39.54% (17/43), 35.57% (15/42), and 26.19% (11/42) in HMVP, MVP, and HVP groups, respectively; no significant difference was detected among the three groups (P >0.05). No significant difference was detected in the median time of remission, median survival time, and 1-, 2-year survival rates among the three groups. Moreover, no significant difference was detected in grade III-IV leukopenia, grade III-IV thrombocytopenia, grade III-IV nausea and vomiting and grade III-IV constipation among the three groups. The response rate of MVP regimen is slightly lower than that of HMVP regimen, but HMVP regimen do not show obvious superiority. It may increase toxicities such as leukopenia, nausea/vomiting, and constipation. The response rate of HVP regimen is slightly lower than that of MVP regimen.

  7. Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Zhigang, E-mail: weizhigang321321@163.com; Ye, Xin, E-mail: yexintaian@aliyun.com; Yang, Xia, E-mail: yangxjinan@163.com; Zheng, Aimin, E-mail: am-zheng@163.com; Huang, Guanghui, E-mail: hgh3612@163.com; Li, Wenhong, E-mail: wenghong-li@163.com; Ni, Xiang, E-mail: asuka2521@hotmail.com; Wang, Jiao; Han, Xiaoying, E-mail: mylittlecarol@sina.com [Shandong Provincial Hospital Affiliated to Shandong University, Department of Oncology (China)

    2015-02-15

    PurposeTo verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.MethodsThirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).ResultsMWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.ConclusionsPatients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

  8. Comparison of Glasgow prognostic score and prognostic index in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

    2015-03-01

    Previous studies have shown that Glasgow prognostic score (GPS) and prognostic index (PI) are also powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to compare the prognostic value between GPS and PI. We enrolled consecutive patients with advanced NSCLC in this prospective cohort. GPS and PI were calculated before the onset of chemotherapy. The prognosis outcomes included 1-, 3-, and 5-year progression-free survival and overall survival (OS). The performance of two scores in predicting prognosis was analyzed regarding discrimination and calibration. 138 patients were included in the study. The area under the receiver operating characteristic curve for GPS predicting 1-year DFS was 0.62 (95 % confidence interval (CI) 0.56-0.68, P statistic showed good fit of the predicted 1-year DFS to the actual 1-year DFS by GPS (χ(2) = 4.326, P = 0.462), while no fit was found between the predicted 1-year DFS and the actual 1-year DFS by PI (χ(2) = 15.234, P = 0.091). Similar results of calibration power were found for predicting 3-year DFS, 5-year DFS, 1-year OS, 3-year OS, and 5-year OS by GPS and PI. GPS is more accurate than PI in predicting prognosis for patients with advanced NSCLC. GPS can be used as a useful and simple tool for predicting prognosis in patients with NSCLC. However, GPS only can be used for preliminary assessment because of low predicting accuracy.

  9. Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer.

    Science.gov (United States)

    Liu, Hui; Zhang, Tiantuo; Ye, Jin; Li, Hongtao; Huang, Jing; Li, Xiaodong; Wu, Benquan; Huang, Xubing; Hou, Jinghui

    2012-10-01

    Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

  10. Utility values associated with advanced or metastatic non-small cell lung cancer: data needs for economic modeling.

    Science.gov (United States)

    Brown, Jacqueline; Cook, Keziah; Adamski, Kelly; Lau, Jocelyn; Bargo, Danielle; Breen, Sarah; Chawla, Anita

    2017-04-01

    Cost-effectiveness analyses often inform healthcare reimbursement decisions. The preferred measure of effectiveness is the quality adjusted life year (QALY) gained, where the quality of life adjustment is measured in terms of utility. Areas covered: We assessed the availability and variation of utility values for health states associated with advanced or metastatic non-small cell lung cancer (NSCLC) to identify values appropriate for cost-effectiveness models assessing alternative treatments. Our systematic search of six electronic databases (January 2000 to August 2015) found the current literature to be sparse in terms of utility values associated with NSCLC, identifying 27 studies. Utility values were most frequently reported over time and by treatment type, and less frequently by disease response, stage of disease, adverse events or disease comorbidities. Expert commentary: In response to rising healthcare costs, payers increasingly consider the cost-effectiveness of novel treatments in reimbursement decisions, especially in oncology. As the number of therapies available to treat NSCLC increases, cost-effectiveness analyses will play a key role in reimbursement decisions in this area. Quantifying the relationship between health and quality of life for NSCLC patients via utility values is an important component of assessing the cost effectiveness of novel treatments.

  11. A Dosimetric Comparison of Dose Escalation with Simultaneous Integrated Boost for Locally Advanced Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Wenjuan Yang

    2017-01-01

    Full Text Available Background. Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC. We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT with a simultaneous integrated boost (SIB in locally advanced NSCLC. Methods. We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy to the planning tumor volume (PTV. In the three SIB groups, the prescribed dose was 69 Gy, 75 Gy, and 81 Gy in 30 fractions to the internal gross tumor volume (iGTV. Results. The SIB-IMRT plans were associated with a significant increase in the iGTV dose (P < 0.05, without increased normal tissue exposure or prolonged overall treatment time. Significant differences were not observed in the dose to the normal lung in terms of the V5 and V20 among the four IMRT plans. The maximum dose (Dmax in the esophagus moderately increased along with the prescribed dose (P < 0.05. Conclusions. Our results indicated that escalating the dose by SIB-IMRT is dosimetrically feasible; however, systematic evaluations via clinical trials are still warranted. We have designed a further clinical study (which is registered with ClinicalTrials.gov, number NCT02841228.

  12. THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

    Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

  13. Survival benefit from chemotherapy with mitomycin-c vinblastine and cisplatin in advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Joaquin, C.F.

    1992-01-01

    Between January 1989 and May 1991 a prospective trial was conducted among the patients in the Lung Center of the Philippines who were diagnosed to have unresectable and metastatic non-small cell lung cancer (NSCLC). There were two groups of patients: those who consented to chemotherapy with the mitomycin, vinblastine and cisplatin regimen (n=31) and those who refused any form of chemotherapy or radiation (n=15). These groups were followed up and compared as to patient characteristics and duration of survival. The results show no identifiable features in the responders and non-responders to chemotherapy which could predict tumor response. The median survival of the untreated group was 15 weeks and that of the treated group was 34 weeks. This was statistically significant. No significant difference in survival between the responders and the non-responders was observed. The objective tumor response rate to the MVP regimen was 25.8%. The most common toxic effects were emesis and hematologic abnormalities. The study recommends the option of chemotherapy with the MVP regimen rather than no treatment at all after considering the risks and benefits for the patient with advanced stage NSCLC. (auth.). 19 refs.; 2 figs.; 4 tabs

  14. Combination of bronchial artery infusion chemotherapy and radiation therapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Li Shuping; Cai Yuecheng; Wang Xiangming; Luo Jianyun; Lian Yingni; Ouyang Mingxin

    2004-01-01

    Objective: To compare the efficacy between bronchial artery infusion (BAI) chemotherapy plus radiation therapy and systemic chemotherapy plus radiation for locally advanced non-small cell lung cancer (NSCLC). Methods: One hundred and twenty-one patients with stage III NSCLC were randomized into treatment group (58 cases) and control group (63 cases). In the treatment group, all patients were administered with BAI for 2-3 sessions, followed by irradiation 4-7 days after BAI. In the control group, altogether 4-6 cycles of standard systemic chemotherapy were given. Radiation was delivered alternately between the cycles of chemotherapy. Results: The short-term, long-term survival, median response duration and median survival time were similar between the two groups, except patients with stage IIIb who had a higher distant metastasis rate in the treatment group. The major side effects of chemotherapy and radiotherapy were hematological, gastrointestinal toxicities, pneumonitis, mediastinitis, and esophagitis, respectively. The side effects were milder, better tolerated and did not influence the regimen schedule in the treatment group, as compared with the control group. Seven patients withdrew from the control group, and in 28 patients, the scheduled chemotherapy and radiation was delayed or canceled. Conclusions: Bronchial artery infusion plus radiation is more advantageous over systemic chemotherapy plus radiation in less toxicities, better compliance, shorter treatment courses and more cost-effectiveness

  15. Induction chemotherapy combined with three-dimensional conformal radiation therapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zheng Aiqing; Yu Jinming; Zhao Xianguang; Wang Xuetao; Wei Guangsheng

    2005-01-01

    Objective: To evaluate the effect and complication of induction chemotherapy combined with three-dimensional conformal radiation therapy (3DCRT) for locally advanced non small cell lung cancer (NSCLC). Methods: Ninety-two such patients were randomized into radiation therapy alone group(RT-, 50 patients) and induction chemotherapy combined radiotherapy group (CMT-, 42 patients). The induction chemotherapy consisted of 2-4 cycles of platinum-based regimen. Results: The overall median survival time was 15 months with 12 months in the RT group and 18 months in the CMT group (P=0.014) respectively. The 1-year overall survival rates were 48.6% and 71.2% in RT and CMT group, respectively (P=0.004). The 2-year survival rates were 20.8% and 37.6% in RT and CMT group, respectively (P=0.041). Treatment was well tolerated and the toxicities were similar in either group. Conclusion: The addition of induction chemotherapy to 3DCRT takes a survival advantage over 3DCRT alone for Stage III NSCLC without increasing toxicities. (authors)

  16. Predicting Radiation Esophagitis Using 18F-FDG PET During Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Mehmood, Qurrat; Sun, Alexander; Becker, Nathan; Higgins, Jane; Marshall, Andrea; Le, Lisa W; Vines, Douglass C; McCloskey, Paula; Ford, Victoria; Clarke, Katy; Yap, Mei; Bezjak, Andrea; Bissonnette, Jean-Pierre

    2016-02-01

    Treatment of locally advanced non-small cell lung cancer with chemoradiotherapy (CRT) is limited by development of toxicity in normal tissue, including radiation esophagitis (RE). Increasingly, (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is being used for adaptive planning. Our aim was to assess changes in esophageal FDG uptake during CRT and relate the changes to the onset and severity of RE. This prospective study in patients with stage II-III non-small cell lung cancer involved serial four-dimensional computed tomography and PET scans during CRT (60-74Gy). RE was recorded weekly using the Common Terminology Criteria for Adverse Events (v4.0), and imaging was performed at weeks 0, 2, 4, and 7. Changes in the esophagus's peak standard uptake value (SUVpeak) were analyzed for each time point and correlated with grade of RE using the Wilcoxon rank-sum test. The volume of esophagus receiving 50 Gy (V50) and volume of esophagus receiving 60 Gy (V60) were correlated with the development of RE, and the C-statistic (area under the curve [AUC]) was calculated to measure predictivity of grade 3 RE. RE developed in 20 of 27 patients (74%), with grade 3 reached in 6 (22%). A significant percentage increase in SUVpeak in the patients with RE was noted at week 4 (p = 0.01) and week 7 (p = 0.03). For grade 3 RE, a significant percentage increase in SUVpeak was noted at week 2 (p = 0.01) and week 7 (p = 0.03) compared with that for less than grade 3 RE. Median V50 (46.3%) and V60 (33.4%) were significantly higher in patients with RE (p = 0.04). The AUC measurements suggested that the percentage change in SUVpeak at week 2 (AUC = 0.69) and V50 (AUC = 0.67) and V60 (AUC = 0.66) were similarly predictive of grade 3 RE. Serial FDG-PET images during CRT show significant increases in SUVpeak for patients in whom RE develops. The changes at week 2 may predict those at risk for the development of grade 3 RE and may be informative for adaptive planning and

  17. Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

    Directory of Open Access Journals (Sweden)

    Guetz S

    2017-02-01

    Full Text Available Sylvia Guetz,1,* Amanda Tufman,2,* Joachim von Pawel,3 Achim Rittmeyer,4 Astrid Borgmeier,2 Pierre Ferré,5 Birgit Edlich,6 Rudolf Maria Huber2 1Ev. Diakonissenkrankenhaus Leipzig, Leipzig, 2University Hospital Munich and Thoracic Oncology Centre Munich, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (DZL CPC-M, Munich, 3Asklepios Fachkliniken Muenchen-Gauting, Gauting, 4Lungenfachklinik Immenhausen, Immenhausen, Germany; 5Pierre Fabre Pharmaceuticals, Oncology Research and Development Center, Toulouse, France; 6Pierre Fabre Pharma GmbH, Freiburg, Germany *These authors contributed equally to this work Micro-abstract: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo in advanced non-small-cell lung cancer (NSCLC. Patients and methods: Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20–50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP, overall survival (OS and tolerability. Results: Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs. Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21

  18. Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy.

    Science.gov (United States)

    Shao, Lan; Zhang, Beibei; He, Chunxiao; Lin, Baochai; Song, Zhengbo; Lou, Guangyuan; Yu, Xinmin; Zhang, Yiping

    2014-01-01

    The preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients. The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model. The objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity. Icotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

  19. Clinical pharmacokinetics, safety, and preliminary efficacy evaluation of icotinib in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Liu, Dongyang; Zhang, Li; Wu, Yiwen; Jiang, Ji; Tan, Fenlai; Wang, Yingxiang; Liu, Yong; Hu, Pei

    2015-09-01

    To receive pharmacokinetics, safety, and anti-tumor activity of icotinib, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in patients with advanced non-small-cell lung cancer (NSCLC). Patients (n=40) with advanced NSCLC were enrolled to receive escalating doses of icotinib, which was administrated on Day 1 followed by 28-day continuous dosing starting from Day 4. Four dosing regimens, 100mg b.i.d., 150 mg b.i.d., 125 mg t.i.d., and 200mg b.i.d. were studied. Pharmacokinetics (PK), safety, and efficacy of icotinib were evaluated. Icotinib was well tolerated in Chinese patients with refractory NSCLC. No toxicity with >3 grades were reported in more than 2 patients under any dose levels. One complete response (3%) and 9 partial responses (23%) were received. Total disease control rate could reach at 73% and median progress-free survival (range) was 154 (17-462) days. PK exposure of icotinib increased with increase of dose in NSCLC patients. Food was suggested to increase PK exposure by ∼30%. Mean t1/2β was within 5.31-8.07 h. No major metabolite (>10% plasma exposure of icotinib) was found in NSCLC patients. Icotinib with up to 400 mg/day exhibited good tolerance and preliminary antitumor activity in Chinese NSCLC patients. Pharmacokinetics of icotinib and 5 major metabolites were fully investigated in NSCLC patients. Optimized biologic dose (OBD) was finally recommended to be 125 mg t.i.d. for the later clinical study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

    Science.gov (United States)

    Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

    2014-08-01

    A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

  1. Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

    International Nuclear Information System (INIS)

    Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Tao, May Lin; Goodman, Karyn A.; Keating, Nancy L.

    2009-01-01

    Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.

  2. Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcome results with rapid arc

    Directory of Open Access Journals (Sweden)

    Fogliata Antonella

    2010-10-01

    Full Text Available Abstract Background To report acute toxicity, initial outcome results and planning therapeutic parameters in radiation treatment of advanced lung cancer (stage III with volumetric modulated arcs using RapidArc (RA. Methods Twenty-four consecutive patients were treated with RA. All showed locally advanced non-small cell lung cancer with stage IIIA-IIIB and with large volumes (GTV:299 ± 175 cm3, PTV:818 ± 206 cm3. Dose prescription was 66Gy in 33 fractions to mean PTV. Delivery was performed with two partial arcs with a 6 MV photon beam. Results From a dosimetric point of view, RA allowed us to respect most planning objectives on target volumes and organs at risk. In particular: for GTV D1% = 105.6 ± 1.7%, D99% = 96.7 ± 1.8%, D5%-D95% = 6.3 ± 1.4%; contra-lateral lung mean dose resulted in 13.7 ± 3.9Gy, for spinal cord D1% = 39.5 ± 4.0Gy, for heart V45Gy = 9.0 ± 7.0Gy, for esophagus D1% = 67.4 ± 2.2Gy. Delivery time was 133 ± 7s. At three months partial remission > 50% was observed in 56% of patients. Acute toxicities at 3 months showed 91% with grade 1 and 9% with grade 2 esophageal toxicity; 18% presented grade 1 and 9% with grade 2 pneumonia; no grade 3 acute toxicity was observed. The short follow-up does not allow assessment of local control and progression free survival. Conclusions RA proved to be a safe and advantageous treatment modality for NSCLC with large volumes. Long term observation of patients is needed to assess outcome and late toxicity.

  3. Health Resource Utilization in Patients with Advanced Non-Small Cell Lung Cancer Receiving Chemotherapy in China.

    Science.gov (United States)

    Shi, Jing; Zhu, Jun

    2016-01-01

    Chemotherapy is the preferred treatment regimen for advanced lung cancer patients. This study investigated the health resources utilized by and medical expenses of patients with non-small cell lung cancer (NSCLC) as well as the influence of various chemotherapy regimens on the final medical costs in China. The aim of this study was to provide physicians with a reference to use as the basis for their choice of treatment. Data were collected from the Shanghai Chest Hospital's medical charts and billing database. The collected patient information included the baseline characteristics, medical history, chemotherapy regimens, and medical costs, which were used to estimate the health resources utilized by patients and the cost of treatment. This study included 328 patients, and the average total medical cost was $US14,165. This cost included drugs, which accounted for as much as 78.91% of the total cost, and chemotherapy drugs, which accounted for 51.58% of total drug expenses. The most frequently utilized chemotherapy drug was carboplatin, and the most expensive chemotherapy drug was erlotinib. In drug combinations, gemcitabine was utilized most frequently, the combination of gemcitabine and paclitaxel was the most expensive, and cisplatin was the least expensive drug. Epidermal growth factor receptor-positive patients were treated with targeted drug therapy (icotinib, erlotinib, and gefitinib). The use of recombinant human endostatin was often combined with a vinorelbine plus cisplatin regimen. Traditional Chinese medicines were the most frequently utilized non-chemotherapy drugs, and these drugs were also the most expensive. The final cost significantly depended on the specific chemotherapy regimen; thus, the rationale and cost of the chemotherapy regimen and adjuvant chemotherapy should be considered in patients with advanced NSCLC.

  4. Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

    OpenAIRE

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2017-01-01

    Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China Background: Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who resp...

  5. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shen YW

    2016-02-01

    Full Text Available Yan-Wei Shen,* Xiao-Man Zhang,* Shu-Ting Li, Meng Lv, Jiao Yang, Fan Wang, Zhe-Ling Chen, Bi-Yuan Wang, Pan Li, Ling Chen, Jin Yang Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background and objective: Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation.Patients and methods: Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1.Results: Among the 35 patients, the tumor objective response rate (ORR and disease control rate were 62.9% (22/35 and 88.6% (31/35, respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months, and median overall survival was 21.0 months (95% CI: 20.1–21.9 months. The most common drug-related toxicities were rashes (eleven patients and diarrhea (nine patients, but these were generally manageable and reversible.Conclusion: Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. Keywords: lung neoplasms, icotinib hydrochloride, first-line treatment

  6. Feasibility of Pencil Beam Scanned Intensity Modulated Proton Therapy in Breath-hold for Locally Advanced Non-Small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Gorgisyan, Jenny; Munck Af Rosenschold, Per; Perrin, Rosalind

    2017-01-01

    PURPOSE: We evaluated the feasibility of treating patients with locally advanced non-small cell lung cancer (NSCLC) with pencil beam scanned intensity modulated proton therapy (IMPT) in breath-hold. METHODS AND MATERIALS: Fifteen NSCLC patients who had previously received 66 Gy in 33 fractions wi...

  7. Non-cross resistant sequential single agent chemotherapy in first-line advanced non-small cell lung cancer patients: Results of a phase II study

    NARCIS (Netherlands)

    V. Surmont; J.G.J.V. Aerts (Joachim); K.Y. Tan; F.M.N.H. Schramel (Franz); R. Vernhout (Rene); H.C. Hoogsteden (Henk); R.J. van Klaveren (Rob)

    2009-01-01

    textabstractBackground. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell

  8. Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy

    NARCIS (Netherlands)

    Wink, Krista C. J.; Belderbos, José S. A.; Dieleman, Edith M. T.; Rossi, Maddalena; Rasch, Coen R. N.; Damhuis, Ronald A. M.; Houben, Ruud M. A.; Troost, Esther G. C.

    2016-01-01

    The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome. A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients).

  9. Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer

    NARCIS (Netherlands)

    Mellema, Wouter W.; Masen-Poos, Lucie; Smit, Egbert F.; Hendriks, Lizza E. L.; Aerts, Joachim G.; Termeer, Arien; Goosens, Martijn J.; Smit, Hans J. M.; van den Heuvel, Michel M.; Wekken, van der Anthonie J.; Herder, Gerarda J. M.; Krouwels, Frans H.; Stigt, Jos A.; van den Borne, Ben E. E. M.; Haitjema, Tjeerd J.; Staal-Van den Brekel, Agnes J.; van Heemst, Robbert C.; Pouw, Ellen; Dingemans, Anne-Marie C.

    2015-01-01

    Objectives: As suggested by in-vitro data, we hypothesize that subtypes of ICRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Methods: Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinumbased chemotherapy, were retrieved

  10. Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Zi; Oh, So Won; Kim, Jin Soo; Kim, Ki Hwan; Kim, Yu Kyeong [SMG-Seoul National University Boramae Medical Center, Seoul (Korea, Republic of)

    2014-12-15

    To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT.One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with %DeltaSUVmean > or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

  11. Erlotinib in the Second/Third Line Treatment of Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yilong WU

    2009-05-01

    Full Text Available Background and objective Erlotinib is a targeted drug for non-small cell lung cancer (NSCLC. The aim of this study is to evaluate the efficacy, influencing factors and toxicity of erlotinib in patients with NSCLC. Methods Patients with NSCLC who had been previously treated with at least one course of platinum based chemotherapyreceived 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression free survival, overall survival and toxicity profile were analyzed. Kaplan-Meier methods was used to analyze the survival rate. Cox regression was used to define the predictive factors. Results Forty-eight patients were enrolled into the study from Dec, 2005 to Sep, 2006. We followed up these patients until 08.Dec.2008. Median follow up time was 30 months. The compliance rate was 100%. The median symptom improving time was 7 days. Partial response 33.4% (16/48, stable disease 22.9% (11/48, and progressive disease 43.7% (21/48. Response rate was 33.4% (16/48. Disease control rate was 56.3% (27/48. One and two-year progression-free survival rates and overall survival rates were 25%(events 36, 8.3% (events 40 and 43.8% (death 27, 20.8% (death 38; three-year overall survival 5.6%. The median progression-free survival time and median overall survival time was 5 months and 8 months, respectively. Performance status was the only predictor for overall survival in the Cox model (P <0.001. Skin toxicity(grade 1 to 3 was found in 93.7% patients. One patient discontinued erlotinib because of perianal abscess. Conclusion Erlotinib is another effective drug for patients with previously chemotherapy advanced NSCLC and accepted toxicity profile.

  12. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    International Nuclear Information System (INIS)

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-01-01

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  13. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  14. Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Bussink, Johan, E-mail: j.bussink@rther.umcn.nl [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

    2012-08-01

    Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

  15. Treatment paradigms for advanced stage non-small cell lung cancer in the era of multiple lines of therapy.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A

    2009-02-01

    The duration of first-line and the timing of second-line therapy for advanced non-small cell lung cancer has been an area of recent investigation. Five trials have been performed that have investigated shorter (3-4 cycles) versus longer duration of platinum-based therapy; four trials revealed an equivalent overall survival with the shorter duration of therapy, and one trial revealed superior survival with the longer duration of therapy. The toxicity and quality of life data has either been equivalent or favored the shorter duration of therapy. Two trials have investigated the timing of a second-line therapy after completion of four cycles of platinum-based therapy versus the standard treatment paradigm of initiating second-line therapy upon disease progression. Both of these trials have revealed a statistically significant improvement in the progression-free survival, and a trend towards improved survival for the earlier use of second-line therapy. Only 50 to 60% of patients on the standard treatment arm initiated second-line therapy, and the promising results observed are most likely related to the fact that a higher percentage of patients received second-line therapy on the experimental arm. Several trials have investigated maintenance chemotherapy, and these trials have not revealed a survival benefit probably due to the fact that many patients experience disease progression or unacceptable toxicity during the initial or maintenance therapy. The addition of a targeted agent (bevacizumab or cetuximab) to the initial chemotherapy and the continuation of the targeted agent after completion of the chemotherapy have yielded superior overall survival in comparison to chemotherapy alone. The incremental benefit of the maintenance therapy with the targeted agent is unknown.

  16. Efficacy of tropisetron in patients with advanced non-small-cell lung cancer receiving adjuvant chemotherapy with carboplatin and taxanes.

    Science.gov (United States)

    Tsavaris, N; Kosmas, C; Kopterides, P; Vadiaka, M; Kosmas, N; Skopelitis, H; Karadima, D; Kolliokosta, G; Tzima, E; Loukeris, D; Pagouni, E; Batziou, E; Xyla, V; Koufos, C

    2008-03-01

    Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.

  17. Are there any dosimetric advantages in using VMAT for treatment of locally advanced non-small cell lung cancer?

    International Nuclear Information System (INIS)

    Rousseau, D.; Krhili, S.; Yossi, S.; Cellier, P.; Paumier, A.; Autret, D.; Dupas, A.; Edouard, M.; Mahe, M.A.; Giraud, P.; Le Pechoux, C.; Denis, F.

    2012-01-01

    Purpose. - To analyse the dosimetric differences between the conventional conformal radiation therapy (CR) and the volumetric modulated arc therapy (VMAT) for non-small-cell locally advanced lung cancer (NSCLC). Patients and methods. - Two plans (CR and VMAT) were calculated for ten NSCLC patients. Dose to PTV, organs at risk and external contours (body), conformity index (PTV volume/volume of the 95% reference isodose) and homogeneity index ([maximal dose - minimal dose]/dose prescription) were compared. Results. - Doses delivered to PTV (homogeneity index, maximal, minimal and mean dose) are similar with both techniques but conformity index is improved by 60% with VMAT: from 0.55 ± 0.07 with CR to 0.89 ± 0.07 with VMAT (P = 0.002). Pulmonary protection is improved with VMAT: with CR and VMAT, respectively, the mean lung dose is 14.1 ± 5.2 Gy and 12.2 ± 4.5 Gy, the lung volume which receives at least 30 Gy (V30) is 20 ± 8% and 14 ± 5%, and the V20 is 24 ± 11% and 20 ± 10% (P = 0.002). The mean dose received by the body is also 9% lower (P = 0.004) and V5 is 13% higher (P = 0.004) with VMAT. V10 and V15 were similar with both modalities. From 20 Gy and higher, irradiated body volume is larger with CR than with VMAT. The relative difference increases with the dose: from 10% for 20 Gy (P = 0.014) up to 39% for 62.7 Gy (P = 0.002). Conclusion. - Compared to CR, VMAT greatly improves conformity and reduces mean dose and dose delivered from 20 Gy and higher to the lungs and the body. (authors)

  18. Molecular profiling in Italian patients with advanced non-small-cell lung cancer: An observational prospective study.

    Science.gov (United States)

    Gobbini, Elisa; Galetta, Domenico; Tiseo, Marcello; Graziano, Paolo; Rossi, Antonio; Bria, Emilio; Di Maio, Massimo; Rossi, Giulio; Gregorc, Vanesa; Riccardi, Ferdinando; Scotti, Vieri; Ceribelli, Anna; Buffoni, Lucio; Delmonte, Angelo; Franchina, Tindara; Migliorino, Maria Rita; Cortinovis, Diego; Pisconti, Salvatore; Bordi, Paola; Catino, Annamaria; Maiello, Evaristo; Arizio, Francesca; Novello, Silvia

    2017-09-01

    Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015. Information regarding molecular profiling and treatment choices were collected. Description of patients' outcome included overall survival (OS), progression-free survival in first (PFS1) and second-line (PFS2). Among 1787 patients enrolled, 1388 (78%) performed at least one molecular analysis during the history of disease: 76% were tested for EGFR, 53% for ALK, 27% for KRAS, 16% for ROS1, 14% for BRAF, 5% for HER2, 4% for MET and 1% for FGFR. The remaining 399 patients (22.3%) did not receive any molecular test. Among patients receiving at least one molecular analysis, 583 (42%) presented a molecular alteration. Considering EGFR mutated and/or ALK rearranged patients (402), for which target agents were routinely reimbursed at time of study in Italy, the 86% received a personalized treatment as first and/or second line: the 90% (286) of EGFR mutants received an EGFR tyrosine kinase inhibitor, mostly gefitinib (41.1%) or afatinib (36.4%) while 74% (62) of ALK translocated patients received an ALK inhibitor, mostly crizotinib (64%). Median OS was 9.34 months (95% CI 8.62-10.0), median PFS1 was 4.61 months (95%CI 4.31-4.84) and median PFS2 was 2.76 months (95%CI 2.57-3.19). In the Italian clinical practice, routine molecular assessment was largely applied in NSCLC patients, according to national guidelines, but a low level of ALK test was reached. Most of EGFR mutants an ALK rearranged patients received a personalized treatment as first and/or second line. Copyright © 2017 Elsevier

  19. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  20. Erlotinib in previously treated non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Smrdel, U.; Kovac, V.

    2006-01-01

    Background. Erlotinib is a novel biological anti-tumour agent in the treatment of advanced non small cell lung cancer. It represents the molecularly-targeted therapy which has been studied extensively. Case report. We present a case of a patient who suffered from advanced non-small-cell lung cancer. After the progress of disease following a prior chemotherapy he was treated with erlotinib with remarkable effect which was shown at chest x ray and symptoms were quite reduced. Conclusions. In selected patients with advanced non-small-cell lung cancer Erlotinib improves survival and symptom control as it results in presented case. (author)

  1. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Melissa Bersanelli

    2014-09-01

    Full Text Available The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group. The other 31 also received subcutaneous IL-2 (GIL-2 group: 1 MIU/m2 (Million International Unit/m2twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%, asthenia/anorexia (6% and diarrhea (7%; patients treated with IL-2 showed grade 2–3 fever (46%, fatigue (21% and arthralgia (13%. In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response and 5.1% (only partial response; a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8 and 4.1 (CI 95% = 2.6–5.7 months; a median overall survival of 20.1 (CI 95% = 5.1–35.1 and 6.9 (CI 95% = 4.9–8.9 months (p = 0.002; and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54 and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60 were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  2. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bersanelli, Melissa, E-mail: melissa.bersanelli@alice.it; Buti, Sebastiano; Camisa, Roberta [Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy); Brighenti, Matteo; Lazzarelli, Silvia [Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona (Italy); Mazza, Giancarlo [Radiology Division, Spedali Civili di Brescia, P.le Spedali Civili,1, 25123 Brescia (Italy); Passalacqua, Rodolfo, E-mail: melissa.bersanelli@alice.it [1Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy)

    2014-09-30

    The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m{sup 2} (Million International Unit/m{sup 2})twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  3. Radiation-induced esophagitis in local advanced non-small cell lung cancer after three-dimensional conformal radiotherapy

    International Nuclear Information System (INIS)

    Tian Dandan; Wang Yuxiang; Qiu Rong; Zhu Shuchai; Tian Xiuming; Qiao Xueying

    2014-01-01

    Objective: To explore radiation-induced esophagitis and its related factors in the patients with local advanced non-small cell lung cancer (NSCLC) which were treated with three-dimensional conformal radiation therapy (3D-CRT). Methods: From January 2001 to December 2008, 203 patients who suffered from stage Ⅲ NSCLC were achieved, including 163 males and 40 females, with a median age of 63 years old, while 79 cases were in stage Ⅲ_a and 124 in stage Ⅲ_b. The equivalent median dose of tumor was 62 Gy(range of 50-78 Gy). Among them, 74 cases were administered with radiotherapy alone, 45 with sequential radiotherapy and chemotherapy, 87 cases with concurrent radiochemotherapy. Radiation esophagitis was evaluated with RTOG standard. The dosimetric parameters was estimated from dose volume histogrma (DVH). The clinical and dosimetric parameters of radiation esophagitis were evaluated by spearman correlatived univariate and Logistic multivariable analysis.Results After radiotherapy, out of 203 patients, 87 had acute radiation esophagitis(RE), 47 in grade 1, 37 in grade 2, and 3 in grade 3 RE. According to spearman correlatived analysis, the correlatived factors included ages, chemotherapy, GTV, PTV, the mean doses of PTV and lung, the max and mean dose of esophagus, V_4_0, V_4_5, V_5_0, V_5_5, V_6_0, length of esophagus (total circumference) treated with 45 Gy (LETT_4_5), and LETT_5_0 (r = -0.162-0.235, P 0.05). There were 21 factors, such as gender, age, smoking, clinical stage, site of tumor, chemotherapy, GTV, PTV, mean dose of PTV and lung, max and mean dose of esophagus, V_4_0-V_6_0 of esophagus, LETT_4_5_-_6_0, incorporated into multivariable analysis, only chemotherapy and V_4_5 of esophagus were independent predicted factors(Wald = 4.626, 9.882, P < 0.05). Conclusions: In local advanced NSCLC after 3D-CRT, chemotherapy(especially concurrent radiochemotherapy) could increase radiation-induced esophagitis. The parameter of DVH could also be used to predict

  4. Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Guowei ZHANG

    2017-04-01

    Full Text Available At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

  5. [Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].

    Science.gov (United States)

    Zhang, Guowei; Wang, Huijuan; Ma, Zhiyong

    2017-04-20

    At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

  6. Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose-Javier; Rodriguez, Ignacio; Gimenez-Capitan, Ana; Molina-Vila, Miquel Angel; Vergnenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

    2016-01-01

    BRCA1 is a main component of homologous recombination and induces resistance to platinum in preclinical models. It has been studied as a potential predictive marker in lung cancer. Several proteins modulate the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damage sites. The combined analysis of multiple components of the pathway leading to the recruitment of BRCA1 at DNA damage sites has the potentiality to improve the BRCA1 predictive model. We retrospectively analyzed 71 paraffin-embedded tumor samples from advanced non-small-cell lung cancer patients treated with first-line platinum based chemotherapy and measured the mRNA expression levels of BRCA1, RNF8, UBC13 and HERC2 using real-time PCR. The mRNA expression was categorized using median value as cut-off point. The median progression-free survival of all 71 patients was 7.2 months whereas the median overall survival of the study population was 10.7 months. Among patients with low BRCA1 expression, the median PFS was 7.4 months in the presence of low HERC2 levels and 5.9 months for patients expressing high HERC2 levels (p = 0.01). The median OS was 15.3 months for patients expressing low levels of both genes and 7.4 months for those with low BRCA1 but high HERC2 (p = 0.008). The multivariate analysis showed that among patients with Eastern Cooperative Oncology Group performance status 0–1, the combined low expression of both BRCA1 and HERC2 clearly reduced the risk of progression (p = 0.03) and of death (p = 0.004). These findings confirm the potentiality of integrated DNA repair components analysis in predicting the sensitivity to platinum in lung cancer. The study indicates a predictive role for HERC2 mRNA expression and paves the way for further refinement of the BRCA1 predictive model. The online version of this article (doi:10.1186/s12885-016-2339-5) contains supplementary material, which is available to authorized users

  7. A methodology to extract outcomes from routine healthcare data for patients with locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Wong, Swee-Ling; Ricketts, Kate; Royle, Gary; Williams, Matt; Mendes, Ruheena

    2018-04-11

    Outcomes for patients in UK with locally advanced non-small cell lung cancer (LA NSCLC) are amongst the worst in Europe. Assessing outcomes is important for analysing the effectiveness of current practice. However, data quality is inconsistent and regular large scale analysis is challenging. This project investigates the use of routine healthcare datasets to determine progression free survival (PFS) and overall survival (OS) of patients treated with primary radical radiotherapy for LA NSCLC. All LA NSCLC patients treated with primary radical radiotherapy in a 2 year period were identified and paired manual and routine data generated for an initial pilot study. Manual data was extracted information from hospital records and considered the gold standard. Key time points were date of diagnosis, recurrence, death or last clinical encounter. Routine data was collected from various data sources including, Hospital Episode Statistics, Personal Demographic Service, chemotherapy data, and radiotherapy datasets. Relevant event dates were defined by proxy time points and refined using backdating and time interval optimization. Dataset correlations were then tested on key clinical outcome indicators to establish if routine data could be used as a reliable proxy measure for manual data. Forty-three patients were identified for the pilot study. The manual data showed a median age of 67 years (range 46- 89 years) and all patients had stage IIIA/B disease. Using the manual data, the median PFS was 10.78 months (range 1.58-37.49 months) and median OS was 16.36 months (range 2.69-37.49 months). Based on routine data, using proxy measures, the estimated median PFS was 10.68 months (range 1.61-31.93 months) and estimated median OS was 15.38 months (range 2.14-33.71 months). Overall, the routine data underestimated the PFS and OS of the manual data but there was good correlation with a Pearson correlation coefficient of 0.94 for PFS and 0.97 for OS. This is a novel approach

  8. Real-life experience of ceritinib in crizotinib-pretreated ALK+ advanced non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Jacques Cadranel

    2018-02-01

    Full Text Available Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase (ALK positive (ALK+ non-small cell lung cancer (NSCLC in a French temporary authorisation for use (TAU study. The French TAU study included crizotinib-pretreated patients with advanced ALK+ or ROS proto-oncogene 1 positive (ROS1+ tumours. Patients received oral ceritinib (750 mg·day−1 as a starting dose and best tumour response (as evaluated by the investigator and safety were reported every 3 months. A total of 242 TAUs were granted from March 12, 2013 to August 05, 2015. Of the 242 patients, 228 had ALK+ NSCLC and 13 had ROS1+ NSCLC. The median age of ALK+ patients (n=214 was 58.5 years, 51.9% were female, 70.8% had an Eastern Cooperative Oncology Group (ECOG performance status (PS of 0–1 and 50.0% had brain metastases. Of the 149 efficacy evaluable ALK+ NSCLC patients, 5.4% had a complete response (CR, 47.0% had a partial response (PR and 22.8% had stable disease (SD. At September 05, 2015, the median duration of ceritinib treatment (n=182 was 3.9 months but 5.5 months for patients (n=71 with a follow-up of ≥12 months. Higher objective response rate (ORR was observed for patients with ECOG PS 0 to 1 (55.0% versus 42.4% and those receiving prior crizotinib for >5 months (51.6% versus 36.1%. Treatment-related adverse events (AEs were reported in 118 of 208 patients (56.7%, the most common being diarrhoea (22.1% and hepatic toxicity (19.7%. Ceritinib (750 mg·day−1 demonstrated efficacy similar efficacy to ASCEND-1, ASCEND-2 and phase 3 ASCEND-5 trials with manageable safety in crizotinib-pretreated patients with ALK+ NSCLC.

  9. Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments.

    Science.gov (United States)

    Alifrangis, Costi; Carter, Philip; Cereser, Biancastella; Chandrasinghe, Pramodh; Belluz, Lisa Del Bel; Lim, Eric; Moderau, Nina; Poyia, Fotini; Tabassum, Neha; Zhang, Hua; Krell, Jonathan; Stebbing, Justin

    2018-02-27

    In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not ( P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group ( P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.

  10. PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data.

    Science.gov (United States)

    Aguiar, Pedro N; De Mello, Ramon Andrade; Hall, Peter; Tadokoro, Hakaru; Lima Lopes, Gilberto de

    2017-05-01

    The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

  11. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Chouaïd C

    2014-12-01

    Full Text Available Christos Chouaïd,1 Perinne Crequit,2 Isabelle Borget,3 Alain Vergnenegre4 1Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal Créteil et Université de Paris Est Créteil, Paris, France; 2Service de Pneumologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France; 3Service de Biostatistique et d’Epidémiologie, Institut Gustave Roussy, Villejuif, France; 4Unité d’Oncologie Thoracique et Cutanée, Centre Hospitalier Universitaire Limoges, Limoges, France Abstract: During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC, with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs per life-year gained (LYG were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY. In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY

  12. Relationship between icotinib hydrochloride exposure and clinical outcome in Chinese patients with advanced non-small cell lung cancer.

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    Ni, Jun; Liu, Dong-Yang; Hu, Bei; Li, Chen; Jiang, Ji; Wang, Han-Ping; Zhang, Li

    2015-09-01

    The current study was conducted to explore the relationship between icotinib hydrochloride exposure and therapeutic effects in Chinese patients with advanced non-small cell lung cancer (NSCLC) who were treated with icotinib hydrochloride. A total of 30 patients with NSCLC who were treated with icotinib hydrochloride were chosen from a single-center, open-label, phase 1 dose escalation clinical trial. Different doses of icotinib hydrochloride were administered orally for 28 consecutive days in different groups until disease progression or unacceptable toxicities occurred. Blood samples were collected during the first treatment cycle (day 1-28) for the pharmacokinetic analysis. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). The plasma concentrations of icotinib hydrochloride were assessed by liquid chromatography-mass spectrometry. Thirty patients with a median age of 56 years old (50% of whom were female) were enrolled. For single-dose treatment, the plasma pharmacokinetics demonstrated a median time to maximum concentration of 0.5 to 4 hours and a mean terminal elimination half-life of 6.21±3.44 hours at the 150-mg dose and 10.1±12.18 hours at the 200-mg dose. For multiple-dose treatment, the last measurable concentration (Clast ) was 708±368.67 ng/mL at the 150-mg every 12 hours, 782.73±618.18 ng/mL at the 200-mg every 12 hours, and 1162±658.44 ng/mL at the 125-mg every 8 hours; the under the concentration curve from time 0 to Clast was 14.5±2.43 hour*mg/mL, 13.2±2.5 hour*mg/mL, and 12.19±2.47 hour*mg/mL, respectively. At the dose of 150 mg every 12 hours, 1 patient with an epidermal growth factor receptor (EGFR) exon 19 deletion achieved a complete response for 10 months; another patient who carried the EGFR exon 19 deletion achieved stable disease for 6 months. Univariate analysis demonstrated that the time to maximum plasma concentration (Tmax ) after a single dose of icotinib hydrochloride was

  13. Effect of Amifostine on Response Rates in Locally Advanced Non-Small-Cell Lung Cancer Patients Treated on Randomized Controlled Trials: A Meta-Analysis

    International Nuclear Information System (INIS)

    Mell, Loren K.; Malik, Renuka; Komaki, Ritsuko; Movsas, Benjamin; Swann, R. Suzanne; Langer, Corey; Antonadou, Dosia; Koukourakis, Michael; Mundt, Arno J.

    2007-01-01

    Purpose: Amifostine can reduce the cytotoxic effects of chemotherapy and radiotherapy in patients with locally advanced non-small-cell lung cancer, but concerns remain regarding its possible tumor-protective effects. Studies with sufficient statistical power to address this question are lacking. Methods and Materials: We performed a meta-analysis of all published clinical trials involving locally advanced non-small-cell lung cancer patients treated with radiotherapy with or without chemotherapy, who had been randomized to treatment with amifostine vs. no amifostine or placebo. Random effects estimates of the relative risk of overall, partial, and complete response were obtained. Results: Seven randomized trials involving 601 patients were identified. Response rate data were available for six studies (552 patients). The pooled relative risk (RR) estimate was 1.07 (95% confidence interval, 0.97-1.18; p = 0.18), 1.21 (95% confidence interval, 0.83-1.78; p = 0.33), and 0.99 (95% confidence interval, 0.78-1.26; p = 0.95) for overall, complete, and partial response, respectively (a RR >1 indicates improvement in response with amifostine compared with the control arm). The results were similar after sensitivity analyses. No evidence was found of treatment effect heterogeneity across the studies. Conclusions: Amifostine has no effect on tumor response in patients with locally advanced non-small-cell lung cancer treated with radiotherapy with or without chemotherapy

  14. Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Shiroyama, Takayuki; Suzuki, Hidekazu; Tamiya, Motohiro; Tamiya, Akihiro; Tanaka, Ayako; Okamoto, Norio; Nakahama, Kenji; Taniguchi, Yoshihiko; Isa, Shun-Ichi; Inoue, Takako; Imamura, Fumio; Atagi, Shinji; Hirashima, Tomonori

    2018-01-01

    Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin ALI ALI ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

    Science.gov (United States)

    Rooney, Claire; Sethi, Tariq

    2015-10-01

    Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

  16. [Prospect and Current Situation of Immune Checkpoint Inhibitors 
in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients].

    Science.gov (United States)

    Wang, Haiyang; Yu, Xiaoqing; Fan, Yun

    2017-06-20

    With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

  17. Insulin-like growth factor 1 receptor expression in advanced non-small-cell lung cancer and its impact on overall survival

    Directory of Open Access Journals (Sweden)

    Humar Mojca

    2017-05-01

    Full Text Available The insulin-like growth factor 1 receptor (IGF1R expression has been addressed as a potential prognostic marker in non-small-cell lung cancer (NSCLC in various studies; however, the associations between IGF1R expression and prognosis of advanced NSCLC patients is still controversial. The aim of our observational, cohort study was to evaluate the expression of IGF1R in advanced NSCLC and its prognostic role. A subgroup analysis was performed to address the influence of pre-existing type 2 diabetes mellitus (T2DM status on IGF1R expression and overall survival (OS.

  18. Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roengvoraphoj, Olarn; Eze, Chukwuka; Li, Minglun; Dantes, Maurice; Taugner, Julian [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); Wijaya, Cherylina [Asklepios Fachkliniken Muenchen-Gauting, Department of Pulmonology, Munich (Germany); Tufman, Amanda; Huber, Rudolf Maria [Ludwig-Maximilians-University of Munich and Thoracic Oncology Centre Munich, Respiratory Medicine and Thoracic Oncology, Internal Medicine V, Munich (Germany); German Centre for Lung Research (DZL CPC-M) (Germany); Belka, Claus; Manapov, Farkhad [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); German Centre for Lung Research (DZL CPC-M) (Germany)

    2018-02-15

    Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG-PET/CT) has an established role in the initial diagnosis and staging of lung cancer. However, a prognostic value of PET/CT during multimodality treatment has not yet been fully clarified. This study evaluated the role of primary tumor metabolic volume (PT-MV) changes on PET/CT before, during, and after chemoradiotherapy (CRT). A total of 65 patients with non-small-cell lung cancer (NSCLC) UICC stage IIIA/B (TNM 7th Edition) were treated with definitive chemoradiotherapy (sequential or concurrent setting). PET/CT was acquired before the start, at the end of the third week, and 6 weeks following CRT. Median overall survival (OS) for the entire cohort was 16 months (95% confidence interval [CI]: 12-20). In all, 60 (92.3%) patients were eligible for pre-treatment (pre-PT-MV), 28 (43%) for mid-treatment (mid-PT-MV), and 53 (81.5%) for post-treatment (post-PT-MV) volume analysis. Patients with pre-PT-MV >63 cm{sup 3} had worse OS (p < 0.0001). A reduction from mid-PT-MV to post-PT-MV of >15% improved OS (p = 0.001). In addition, patients with post-PT-MV > 25 cm{sup 3} had significantly worse outcome (p = 0.001). On multivariate analysis, performance status (p = 0.002, hazard ratio [HR] 0.007; 95% CI 0.00-0.158), pre-PT-MV1 < 63 cm{sup 3} (p = 0.027, HR 3.98; 95% CI 1.17-13.49), post-PT-MV < 25 cm{sup 3} (p = 0.013, HR 11.90; 95% CI 1.70-83.27), and a reduction from mid-PT-MV to post-PT-MV > 15% (p = 0.004, HR 0.25; 95% CI 0.02-0.31) correlated with improved OS. Our results demonstrated that pre- and post-treatment PT-MV, as well as an at least 15% reduction in mid- to post-PT-MV, significantly correlates with OS in patients with inoperable locally advanced NSCLC. (orig.) [German] Die kombinierte Positronenemissionstomographie (PET) mit {sup 18}F-2-Fluor-2-desoxy-D-Glukose und Computertomographie ({sup 18}F-FDG-PET/CT) hat sich in der initialen

  19. First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Gupta N

    2013-12-01

    Full Text Available Neha Gupta, Hassan Hatoum, Grace K DyDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USAAbstract: Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007 is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel. A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.Keywords: ABI-007, Abraxane, nab

  20. Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

    Science.gov (United States)

    Song, Gaoguang; Liu, Yujie; Wang, Yanying; Ren, Guanjun; Guo, Shuai; Ren, Junling; Zhang, Li; Li, Zhili

    2015-02-02

    Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression. Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis. Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks). The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. The relationship between glasgow prognostic score and serum tumor markers in patients with advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

    2015-01-01

    Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated

  2. [Clinical efficacy and adverse effects of taxol plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma].

    Science.gov (United States)

    Wang, Xiao-Yun; Zhao, Yu-Liang

    2010-12-21

    To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. A total of 86 patients with advanced non-small-cell lung carcinoma with a histologically confirmed diagnosis at our department were treated with at least two cycles of drug therapy according to the WHO standard. There were 43 cases in TP group and 43 cases in GP group. TP group: taxol 150 mg/m(2), d1, carboplatin 300 mg/m(2) in d1; GP group: gemcitabine 1000 mg/m(2), 30 min, d1, 8, carboplatin 300 mg/m(2) in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. When TP and GP groups were compared, the effective rate was 44.2% vs 39.5%; disease control rate (CR + PR + SD): 81.4% vs 74.4%; median time to progress (TTP): 4.6 vs 4.5 months; medium survivals: 8.6 vs 8.8 months; 1-year survival rates: 17.2% vs 18.1%; 2-year survival rates: 8% vs 10%. The statistic analysis showed that the two groups had no significant difference. The main cytotoxicities of GP and TP groups were predominantly thrombocytopenia and leucopenia respectively. The two groups had no significant statistical difference. The incidences of allergen, alopecia and peripheral neurotoxicity were higher in the TP group. The two groups had statistical difference. Tolerance was excellent in both groups. The therapeutic effect and tolerance are excellent for advanced non-small cell lung carcinoma. The efficacy and survival rate of two groups show no statistical difference.

  3. Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Nikaedo Sueli M

    2004-09-01

    Full Text Available Abstract Background Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC can be achieved with cisplatin-based chemotherapy (CT, its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. Methods In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years, younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2, and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2. We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Results Analysis was by intention to treat. Main toxicities (grade 3–4 was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP and overall survival (OS were 27.0 (95% CI: 10.1 to 43.7 weeks and 30.1 (95% CI: 24.4 to 35.8 weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%, with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Conclusion Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions.

  4. Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Pereira, José Rodrigues; Martins, Sandro J; Nikaedo, Sueli M; Ikari, Flora K

    2004-01-01

    Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m 2 , on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m 2 or 90 mg/m 2 ), and older patients were allocated to lower cisplatin doses (60 mg/m 2 or 70 mg/m 2 ). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Analysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions

  5. Involved-Field Radiotherapy versus Elective Nodal Irradiation in Combination with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study

    Science.gov (United States)

    Chen, Ming; Bao, Yong; Ma, Hong-Lian; Wang, Jin; Wang, Yan; Peng, Fang; Zhou, Qi-Chao; Xie, Cong-Hua

    2013-01-01

    This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study. PMID:23762840

  6. Study of efficacy and toxicity of hypofractionated thoracic radiotherapy 17 gray in 2 fractions for palliation in advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Arif, S.; Rasul, S.; Haider, N.; Mahmood, A.; Syed, A.S.; Nadeem, M.

    2012-01-01

    Objective: To determine the efficacy and toxicity of hypofractionated thoracic radiotherapy 17 Gray (Gy) in 2 fractions for palliation in advanced non-small-cell lung carcinoma. Study design: A quasi-experimental study. Place and duration of study: Oncology department, Combined Military Hospital, Rawalpindi, from 4th July 2008 to 4th Nov 2009. Material and Methods: Fifty four patients with histologically and/or cytologically confirmed unresectable stages III and IV non small cell lung cancer, with performance status 2 or 3 and expected survival > 2 months were treated with megavoltage radiation therapy 17 Gy in 2 fractions one week apart, with symptoms due to intrathoracic disease (cough, dyspnea and hemoptysis) and toxicity due to radiation therapy (dysphagia secondary to esophagitis) assessed as per common toxicity criteria adverse event version 3.0 on day 0 before treatment and day 30 after start of treatment. Results: Grades of cough, hemoptysis and dyspnea showed significant improvement after treatment (p<0.001). A total of 42.68% patients showed an improvement in grade of cough (23 out of 54 patients), 85.7% of patients showed improvement in grade of hemoptysis (36 out of 42 patients) and 55.65% patients showed improvement in grade of dyspnea (30 out of 54 patients). Twenty two point two percent patients (12 out of 54) showed increase in grade of dysphagia. Although, there was a statistically significant increase in grade of dysphagia after treatment but it was limited to grade 1 and 2 only. Considering that no patient had grade 3 or 4 dysphagia, this toxicity was acceptable. Conclusion: Based on our results hypofractionated thoracic radiotherapy, 17 Gy in 2 fractions, is effective with acceptable toxicity in palliation in advanced non small cell lung cancer and is recommended as it will result in shorter duration of hospital stay and low hospital stay charges. (author)

  7. Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing.

    Science.gov (United States)

    Moreira, Andre L; Thornton, Raymond H

    2012-09-01

    In light of recent advances in individualized therapy for non-small-cell lung cancer (NSCLC), molecular and histologic profiling is essential for guiding therapeutic decisions. Results of these analyses may have implications for both response (eg, molecular testing for EGFR [epidermal growth factor receptor] mutations) and safety (eg, contraindications for squamous histology) in NSCLC. Most patients with NSCLC present with unresectable advanced disease; therefore, greater emphasis is being placed on minimally invasive tissue acquisition techniques, such as small biopsy and cytology specimens. Due to the need for increasing histologic and molecular information and increasingly smaller tissue sample sizes, efforts must be focused on optimizing tissue acquisition and the development of more sensitive molecular assays. Recent advances in tissue acquisition techniques and specimen preservation may help to address this challenge and lead to enhanced personalized treatment in NSCLC. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Treatment decision-making for advanced non-small cell lung cancer and differences among European countries: 1st AIOT-ETOP meeting.

    Science.gov (United States)

    Gridelli, Cesare; Stahel, Rolf; Besse, Benjamin; Ciardiello, Fortunato; Felip, Enriqueta; Gasparini, Stefano; Graziano, Paolo; Rossi, Antonio; de Marinis, Filippo

    2011-12-01

    The Italian Association of Thoracic Oncology (AIOT) and the European Thoracic Oncology Platform (ETOP) realized the first conjunct educational meeting, open to European oncologists involved in the treatment of thoracic malignancies, entitled "Advanced non-small cell lung cancer: new perspectives in first-line setting". The educational meeting included 8 interactive talks, held by European key opinion leaders, and 5 related clinical cases in which the attendees, divided in working tables based on their country origin, were involved for interactive discussion. The aim of this course was to elucidate the differences or similarities among the European countries in the first-line treatment of patients affected by advanced non-small cell lung cancer (NSCLC). Twenty-two attendees of the following countries participated: Austria, France, Italy, Spain, Swiss, and UK. As expected, some discrepancies between the groups were identified concerning the approach to the diagnostic phase, the choice of first-line regimen, the duration of treatment and the use of maintenance therapy. These discrepancies were mainly due to familiarity with specific therapies and lack of access to certain therapies due to local regulatory issues. The European Medicine Agency grants marketing of drugs in all Europe, regulatory agency of each country can register the drug, but can also deny public reimbursement thus restricting the options of the oncologist. The European Oncology Associations should join to their effort to achieve a uniform access to the cancer therapy for all patients in Europe. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  10. A willingness-to-pay study of oral epidermal growth factor tyrosine kinase inhibitors in advanced non-small cell lung cancer.

    Science.gov (United States)

    Leighl, Natasha B; Tsao, W Stephen; Zawisza, Dianne L; Nematollahi, Mahsan; Shepherd, Frances A

    2006-01-01

    Oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are new agents in the treatment of advanced non-small cell lung cancer (NSCLC). Phase II studies demonstrate objective tumor responses and symptom improvement, combined with minimal toxicity and the convenience of an oral agent. We evaluated patient utility through willingness-to-pay (WTP) for these agents in the treatment of advanced NSCLC in Canada. Advanced NSCLC patients and healthy subjects participated in a structured interview and bidding exercise, reviewing current evidence supporting EGFR TKI therapy in advanced NSCLC and patient willingness-to-pay for treatment. Fifty-seven patients and 54 healthy subjects participated. The median amount both groups were willing to pay for a month of oral EGFR TKI therapy was $100 CAD (range $0-5000 per month). A minority of NSCLC patients received employment income, the majority relying on disability, pension income, and social assistance for financial support. Affordability of these agents was a key concern for both advanced NSCLC patients and healthy subjects. Univariate predictors of WTP included marital status, prior chemotherapy treatment, receiving pension income or financial social assistance. In multivariate analysis, only prior chemotherapy remained a significant predictor of WTP (p=0.049). Both advanced NSCLC patients and healthy subjects feel oral EGFR TKIs are worth paying for in the treatment of advanced NSCLC, but are willing to pay only a fraction of the market price. As many advanced NSCLC patients are financially disadvantaged, the potential for restricted access to newer therapies is of concern.

  11. Gender, histology, and time of diagnosis are important factors for prognosis: analysis of 1499 never-smokers with advanced non-small cell lung cancer in Japan.

    Science.gov (United States)

    Kawaguchi, Tomoya; Takada, Minoru; Kubo, Akihito; Matsumura, Akihide; Fukai, Shimao; Tamura, Atsuhisa; Saito, Ryusei; Kawahara, Masaaki; Maruyama, Yosihito

    2010-07-01

    There has been a growing interest in lung cancer in never-smokers. Utilizing a database from the National Hospital Study Group for Lung Cancer, information for never-smokers and ever-smokers with advanced non-small cell lung cancer was obtained from 1990 to 2005, including clinicopathologic characteristics, chemotherapy response, and survival data. Time of diagnosis was classified into two periods: 1990-1999 and 2000-2005. Multivariate analysis was performed using the Cox regression and logistic regression method, including gender, age, performance status, histology, stage, and period of diagnosis. There were 1499 never-smokers and 3455 ever-smokers with advanced stage IIIB and IV diseases who received cytotoxic chemotherapy. Never-smokers generally included more females, were younger, with better performance status and more adenocarcinoma diagnosed (p time of diagnosis are important factors for prognosis in these patients.

  12. A comprehensive review of nongenetic prognostic and predictive factors influencing the heterogeneity of outcomes in advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Cuyún Carter G

    2014-10-01

    Full Text Available Gebra Cuyún Carter,1 Amy M Barrett,2 James A Kaye,3 Astra M Liepa,1 Katherine B Winfree,1 William J John1 1Eli Lilly and Company, Indianapolis, IN, USA; 2RTI Health Solutions, Research Triangle Park, NC, USA; 3RTI Health Solutions, Waltham, MA, USA Abstract: While there have been advances in treatment options for those with advanced non-small-cell lung cancer, unmet medical needs remain, partly due to the heterogeneity of treatment effect observed among patients. The goals of this literature review were to provide updated information to complement past reviews and to identify a comprehensive set of nongenetic prognostic and predictive baseline factors that may account for heterogeneity of outcomes in advanced non-small-cell lung cancer. A review of the literature between 2000 and 2010 was performed using PubMed, Embase, and Cochrane Library. All relevant studies that met the inclusion criteria were selected and data elements were abstracted. A classification system was developed to evaluate the level of evidence for each study. A total of 54 studies were selected for inclusion. Patient-related factors (eg, performance status, sex, and age were the most extensively researched nongenetic prognostic factors, followed by disease stage and histology. Moderately researched prognostic factors were weight-related variables and number or site of metastases, and the least studied were comorbidities, previous therapy, smoking status, hemoglobin level, and health-related quality of life/symptom severity. The prognostic factors with the most consistently demonstrated associations with outcomes were performance status, number or site of metastases, previous therapy, smoking status, and health-related quality of life. Of the small number of studies that assessed predictive factors, those that were found to be significantly predictive of outcomes were performance status, age, disease stage, previous therapy, race, smoking status, sex, and histology. These

  13. Randomized Study of Concurrent Carboplatin, Paclitaxel, and Radiotherapy with or Without Prior Induction Chemotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Gouda, Y.S.; Eldeeb, N.A.; Omar, A.M.; Kohail, H.M.; El-Geneidy, M.M.; Elkerm, Y.M.

    2006-01-01

    Background: Multiple concepts of combined modality therapy for locally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemo-radiotherapy, and radiation only. To date, combined modality therapy specially the use of concomitant chemo-radiotherapy has led to promising results and was shown to be superior to radiotherapy alone in phase II studies. However the optimum chemo-therapeutic regimen to be used as well as the benefit of induction chemotherapy before concomitant chemo-radiotherapy are yet to be determined. Based on these observations, we investigated the use of paclitaxel and carboplatin concomitantly with radiotherapy and the benefit of prior two cycles induction chemotherapy. Materials and Methods: In this trial 50 patients with locally advanced inoperable non small cell lung cancer, good performance status and minimal weight loss have been randomized into 3 groups each of 20 patients. Group A received induction 2 cycles paclitaxel (175 mg/m 2 ) and carboplatin (AUC 6) on day I and 28 th followed by concomitant paclitaxel (45 mg/m 2 ) and carboplatin (AUC 2) weekly with radiotherapy. Group B received concomitant carboplatin, paclitaxel (same doses as in group A) and radiotherapy with no prior induction chemotherapy. Group C received only radiotherapy to a total dose of 60 Gy in conventional fractionation. Results: A total of 60 patients were enrolled in this study between 1998 and 2000. Pretreatment characteristics, including age, gender, performance status, histological features and stage were comparable in each group. The incidence of oesophagi tis was significantly higher in group A and B than in group C (ρ=0.023). Hematological toxicities was also significantly higher in group A and B than in group C (ρ=0.003). The response rate was significantly higher in group A and B than in group C (75%,79%, and 40% respectively) (ρ =0.020). The time to in-field progresion was significantly

  14. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  15. Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Lai XX

    2016-04-01

    Full Text Available Xi-Xi Lai, Ren-Ai Xu, Yu-Ping Li, Han Yang Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC. We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC.Methods: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials.Results: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55, hypertension (RR =5.34, and hemorrhagic events (RR =2.61. No statistically significant differences were found for gastrointestinal perforation (P=0.60, arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively, or fatal events (P=0.29.Conclusion: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. Keywords: toxicities, angiogenesis inhibitors, non-small-cell lung carcinoma, meta-analysis, safety

  16. Advanced non-small cell lung cancer in elderly patients: The standard every 3-weeks versus weekly paclitaxel with carboplatin

    Directory of Open Access Journals (Sweden)

    Hala Mohamed El-Shenshawy

    2012-10-01

    Conclusions: Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile.

  17. Preliminary Safety, Pharmacokinetics, and Efficacy of Regorafenib, Cisplatin, and Pemetrexed in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancers.

    Science.gov (United States)

    Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A; Gettinger, Scott N

    2015-11-01

    Regorafenib is an oral multitargeted kinase inhibitor with potent antiangiogenic activity. In this phase I trial we evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nonsquamous non-small-cell lung cancers (nsNSCLCs). Nine patients enrolled before premature termination of the study. Five of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range, 1.5-15.1 months). Regorafenib had acceptable tolerability and minor pharmacokinetic interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. The combination of bevacizumab, an antiangiogenesis agent, with cytotoxic chemotherapy improves survival in patients with advanced nonsquamous non-small-cell lung cancers (nsNSCLCs). Regorafenib is an oral multitargeted kinase inhibitor with potent antiangiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. In this phase I trial we evaluated the safety, pharmacokinetics (PK), and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Chemotherapy-naive patients with advanced nsNSCLCs were treated with regorafenib 60 mg/d continuously and cisplatin 75 mg/m(2) with pemetrexed 500 mg/m(2) once every 21 days for up to 6 cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Nine patients enrolled before premature termination of the study because of slow recruitment and a change in the development strategy of regorafenib by the study sponsor. Five patients experienced at least 1 treatment-related Grade 3 adverse event. No Grade 4 or 5 toxicity occurred. Five of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range, 1.5-15.1 months). Minor PK interactions between regorafenib and chemotherapy were observed. Regorafenib had acceptable

  18. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    International Nuclear Information System (INIS)

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance

  19. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial.

    Science.gov (United States)

    Shi, Yuankai; Zhang, Li; Liu, Xiaoqing; Zhou, Caicun; Zhang, Li; Zhang, Shucai; Wang, Dong; Li, Qiang; Qin, Shukui; Hu, Chunhong; Zhang, Yiping; Chen, Jianhua; Cheng, Ying; Feng, Jifeng; Zhang, Helong; Song, Yong; Wu, Yi-Long; Xu, Nong; Zhou, Jianying; Luo, Rongcheng; Bai, Chunxue; Jin, Yening; Liu, Wenchao; Wei, Zhaohui; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Dai, Hong; Jiao, Shunchang; Wang, Jie; Liang, Li; Zhang, Weimin; Sun, Yan

    2013-09-01

    Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug

  20. A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Ahn, Hee Kyung; Jung, Minkyu; Sym, Sun Jin; Shin, Dong Bok; Kang, Shin Myung; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Cho, Eun Kyung

    2014-08-01

    Genexol-PM is a Cremorphor EL (CrEL)-free polymeric micelle formulation of paclitaxel that allows higher-dose administration with less hypersensitivity. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients as a first-line treatment. This is a prospective, single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on day 1 and day 8 of a 3-week cycle. Six cycles of chemotherapy were planned unless there was disease progression. The primary endpoint was overall response rate. Forty-three patients received the study drugs with a median of 4 cycles per patient (range 1-6). The overall response rate was 46.5%. The median progression-free survival was 4.0 months (95% CI 2.0-6.0 months), and median overall survival was 14.8 months (95% CI 9.1-20.5 months). The most common toxicities were anemia (n = 29, 67%), asthenia (n = 17, 40%), myalgia (n = 16, 37%), peripheral neuropathy (n = 15, 35 %), and diarrhea (n = 12, 30%). The most common grade 3/4 adverse events were neutropenia (n = 7, 16%) and pneumonia (n = 5, 12%). Two patients died of pneumonia and dyspnea. CrEL-free paclitaxel in combination with gemcitabine demonstrated favorable antitumor activity with little emetogenicities in non-small cell lung cancer patients. However, frequent grade 3/4 toxicities were observed, and safety should be evaluated thoroughly in future studies.

  1. The emerging role of ALK inhibitors in the treatment of advanced non-small cell lung cancer.

    Science.gov (United States)

    Galetta, Domenico; Rossi, Antonio; Pisconti, Salvatore; Colucci, Giuseppe

    2012-04-01

    Most NSCLC patients are diagnosed in the advanced stage of the disease. Recently, chemotherapeutic agents have reached a plateau of effectiveness. Increased understanding of cancer biology has revealed several potential therapeutic strategies that have led to marketing of new biologic agents. The echinoderm microtubule-associated protein like-4-anaplastic lymphoma kinase (EML4-ALK) fusion oncogene represents one of the newest molecular targets in NSCLC, identifying a subset of NSCLC patients characterized by distinct clinicopathological features. The available results concerning ALK inhibitors for the treatment of advanced NSCLC patients. An electronic search was used to retrieve the articles addressing this topic. In a pivotal Phase I clinical trial, crizotinib (PF-02341066), a small-molecule ALK inhibitor, demonstrated impressive antitumor activity in the majority of NSCLC patients with ALK fusions. Phase III randomized trials investigating crizotinib in this subgroup of patients are ongoing. If the results from these large international trials confirm the efficacy of crizotinib in the subset of patients, the next few years could see the treatment of advanced NSCLC patients with ALK fusions. Specific inhibitors would realize the so called personalized medicine in subsets of this disease.

  2. The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

    Science.gov (United States)

    Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

    2010-01-01

    Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

  3. Treatment Choice for Advanced Non-small Cell Lung Cancer Patients Who Had Gradual Progression After EGFR-TKIs: 32 Cases Report

    Directory of Open Access Journals (Sweden)

    Lin LIN

    2013-10-01

    Full Text Available Background and objective The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in the treatment of the advanced non-small cell lung cancer (NSCLC, especially in the adenocarcinoma patients with activating EGFR mutations. But there is no published overview of the following treatment. This report through observing the efficacy, toxicity and overall survival of different treatments to the advanced NSCLC patients who had gradual progression after EGFR-TKIs, evaluates the influence of the continued treatment and switching chemotherapy. Methods Retrospective review is conducted on 32 cases of advanced NSCLC patients who experienced treatment failure of EGFR-TKIs. One group accepted the continued treatment and the other group accepted the switching chemotherapy. Results The median overall survival of the continued treatment group is 36.0 months. The respose rate of the switching chemotherapy group is 43.75%, and clinical benefit rate (complete and partial response and stable disease is 87.5%. The median overall survival is 15.5 months. The main toxicities are nausea, vomiting and hematological toxicities. Conclusion For the advanced NSCLC patients who had gradual progression after EGFR-TKIs, the continued treatment is one of the acceptable choices.

  4. High-dose cisplatin with dipyridamole in advanced non-small cell lung cancer. A Grupo Oncológico Cooperativo del Sur study.

    Science.gov (United States)

    Vallejo, C T; Rabinovich, M G; Perez, J E; Rodriguez, R; Machiavelli, M R; Leone, B A; Romero, A D; Lacava, J A; Cuevas, M A; Langhi, M J

    1995-06-01

    From March 1991 to October 1992, 41 patients with advanced non-small cell lung cancer (NSCLC) (20 stage IIIB and 21 stage IV) received a regimen consisting of cisplatin (CP) 100 mg/m2 i.v. days 1 and 8, and dipyridamole (DPD) 100 mg p.o. 75 minutes before CP, and then at hours 6, 12, and 18 as first-line chemotherapy. Cycles were repeated every 28 days for a total of 3. Median age was 56 years (range: 40-70). All patients had a performance status 0 to 1 and a weight loss < or = 10%. Squamous-cell carcinoma was diagnosed in 19 patients; adenocarcinoma in 16, and large-cell carcinoma in 6. A total of 37 patients were fully evaluable for response, whereas 39 were assessable for toxicity. No complete responses were observed: 5 patients (14%) achieved partial response; 23 patients (62%) showed no change, and progressive disease was observed in 9 (24%). The median time to treatment failure was 4 months, whereas median survival was 8 months. The average dose intensity received at the end of the third course of therapy was 46 mg/m2/week. There were no drug-related deaths. Toxicity was mild to moderate, with a high incidence of ototoxicity (54%) and emesis (67%). In conclusion, these results failed to demonstrate any significant advantage from a high-dose CP regimen modulated by DPD in patients with advanced NSCLC.

  5. A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

    2016-11-01

    This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher

  6. [Advances in the Research of the Regulation of Chinese Traditional Medicine Monomer and Its Derivatives on Autophagy in Non-small Cell Lung Cancer].

    Science.gov (United States)

    Xiang, Meiyi; Li, Ruilei; Zhang, Zhiwei; Song, Xin

    2017-03-20

    The high morbidity and mortality of non-small cell lung cancer (NSCLC) did influence the quality of life of tumor patients world-wide. There is an urgent need to develop new therapies that have high anti-tumor activity and low toxicity side effects. It is widely accepted that autophagy can play diverse roles in carcinogenesis, such as induces pro-death of lung cancer cells or helps the escape from cell death, making it become a proper anticancer target. It's believed that various monomers of Chinese traditional medicine closely correlates to anti-NSCLC activities, and that even could affect the acquired multiple drug resistance (MDR). Furthermore, autophagy might be the underling mechanisms which could play a role as the candidate targets of natural active compounds. Recent studies of terpenoids, alkaloid, dietary polyphenols, saponins and other active ingredients that extracted from a large variety of herbs suggest that different monomer compounds could either regulate the activity of pro-death autophagy or influence the level of protective autophagy of NSCLC cells, thus changing their drug sensitivity and cell viability. This paper aims to give a systemic description of the latest advances about natural compounds and their derivatives that involved in tumorigenesis of NSCLC via inducing the autophagy.

  7. Smoking History Predicts Sensitivity to PARP Inhibitor Veliparib in Patients with Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Reck, Martin; Blais, Normand; Juhasz, Erzsebet; Gorbunova, Vera; Jones, C Michael; Urban, Laszlo; Orlov, Sergey; Barlesi, Fabrice; Kio, Ebenezer; Keilholz, Ulrich; Qin, Qin; Qian, Jiang; Nickner, Caroline; Dziubinski, Juliann; Xiong, Hao; Mittapalli, Rajendar K; Dunbar, Martin; Ansell, Peter; He, Lei; McKee, Mark; Giranda, Vincent; Ramalingam, Suresh S

    2017-07-01

    Tobacco-related NSCLC is associated with reduced survival and greater genomic instability. Veliparib, a potent poly(adenosine diphosphate-ribose) polymerase inhibitor, augments platinum-induced DNA damage. A phase 2 trial of untreated advanced NSCLC showed a trend for improved outcomes (hazard ratio [HR] = 0.80, 95% confidence interval: 0.54-1.18, p = 0.27 for overall survival and HR = 0.72, 95% CI: 0.45-1.15, p = 0.17 for progression-free survival) when veliparib was added to carboplatin/paclitaxel. Here we report an exploratory analysis by smoking history. Patients were randomized 2:1 to receive carboplatin/paclitaxel with veliparib, 120 mg (n = 105), or placebo (n = 53). Patients were stratified by histologic subtype and smoking history (recent smokers [n = 95], former smokers [n = 42], and never-smokers [n = 21]). Plasma cotinine level was measured as a chemical index of smoking. Mutation status was assessed by whole exome sequencing (n = 38). Smoking history, histologic subtype, age, Eastern Cooperative Oncology Group performance status, sex, and geographic region predicted veliparib benefit in univariate analyses. In multivariate analysis, history of recent smoking was most predictive for veliparib benefit. Recent smokers treated with veliparib derived significantly greater progression-free survival and overall survival benefits (HR = 0.38 [p Smoking history predicted for efficacy with a veliparib-chemotherapy combination; toxicity was acceptable regardless of smoking history. A prespecified analysis of recent smokers is planned for ongoing phase 3 studies of veliparib in NSCLC. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  8. Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer

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    Veldore VH

    2018-01-01

    Full Text Available Vidya H Veldore,1,* Anuradha Choughule,2,* Tejaswi Routhu,1 Nitin Mandloi,1 Vanita Noronha,2 Amit Joshi,2 Amit Dutt,3 Ravi Gupta,1 Ramprasad Vedam,1 Kumar Prabhash2 1MedGenome Labs Private Ltd,, Bangalore, India; 2Tata Memorial Centre, Parel, Mumbai, India; 3The Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai, Maharashtra, India *These authors contributed equally to this work Abstract: Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA, from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS for EGFR mutation testing in non-small cell lung cancer (NSCLC. A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0.01%. Benchmarking allele specific real time PCR as one of the standard methods for tissue-based EGFR mutation testing, the ctDNA NGS test was validated on all the plasma derived cell-free DNA samples. We observed a high concordance (96.96% between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the EGFR gene. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the assay were 91.1%, 100% 100%, 95.6%, and 97%, respectively. A false negative rate of 3% was observed. A subset of mutations was also verified on droplet digital PCR. Sixteen percent EGFR mutation positivity was observed in patients where only liquid biopsy was available, thus creating options for targeted therapy. This is the first and largest study from India, demonstrating successful validation of circulating cell-free DNA as a clinically

  9. Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

    International Nuclear Information System (INIS)

    Russo, Francesca; Bearz, Alessandra; Pampaloni, Gianni; The investigators of the Italian Pemetrexed monotherapy of NSCLC group

    2008-01-01

    The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC. Overall, 95 patients received pemetrexed 500 mg/m 2 i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria. Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression. Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities

  10. Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

    International Nuclear Information System (INIS)

    Farina, Davide; Morassi, Mauro; Maroldi, Roberto; Roca, Elisa; Tassi, Gianfranco; Cavalleri, Giuseppe

    2013-01-01

    To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. (orig.)

  11. Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

    International Nuclear Information System (INIS)

    Manapov, Farkhad; Roengvoraphoj, Olarn; Li, Ming Lun; Eze, Chukwuka

    2017-01-01

    Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] ≤ 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/ CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 ≤ 1 L)

  12. Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

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    Manapov, Farkhad; Roengvoraphoj, Olarn; Li, Ming Lun; Eze, Chukwuka [Dept. of Radiation Oncology, Ludwig-Maximilian University of Munich, Munich (Germany)

    2017-06-15

    Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] ≤ 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/ CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 ≤ 1 L)

  13. Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiao ZHAO

    2012-01-01

    Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

  14. The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H

    2015-05-01

    The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

  15. Regional hyperthermia combined with radiotherapy for locally advanced non-small cell lung cancers. A multi-institutional prospective randomized trial of the International Atomic Energy Agency

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Hiraoka, Masahiro; Zeng Zhifan; Oliynychenko, P.; Park, Jeong-Ho; Choi, Ihl-Bohng; Tatsuzaki, Hideo; Tanaka, Yoshiaki

    2007-01-01

    An International Atomic Energy Agency (IAEA)-sponsored, multi-institutional prospective randomized trial was conducted to clarify whether the combination of hyperthermia and radiotherapy improves the local response rate of locally advanced non-small cell lung cancer (NSCLC) compared with that obtained by radiotherapy alone. Between October 1998 and April 2002, 80 patients with locally advanced NSCLC were randomized to receive either standard radiation therapy alone (RT) or radiation therapy combined with hyperthermia (RT+HT). The primary endpoint was the local response rate. The secondary endpoints were local progression-free survival and overall survival. The median follow-up period was 204 days for all patients and 450 days for surviving patients. There were no significant differences between the two arms with regard to local response rate (P=0.49) or overall survival rate (P=0.868). However, local progression-free survival was significantly better in the RT+HT arm (P=0.036). Toxicity was generally mild and no grade 3 late toxicity was observed in either arm. Although improvement of local progression-free survival was observed in the RT+HT arm, this prospective randomized study failed to show any substantial benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced NSCLC. (author)

  16. Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2011-02-01

    Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

  17. Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

    Science.gov (United States)

    Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

    2010-11-01

    Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Preliminary safety, pharmacokinetics, and efficacy of regorafenib, cisplatin, and pemetrexed in patients with advanced non-squamous non-small cell lung cancers

    Science.gov (United States)

    Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A.; Gettinger, Scott N.

    2016-01-01

    Structured Abstract Purpose The addition of bevacizumab, an anti-angiogenesis agent, to cytotoxic chemotherapy improves survival in patients with advanced non-squamous non-small cell lung cancers (nsNSCLCs). Regorafenib is an oral multi-targeted kinase inhibitor with potent anti-angiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. This phase I trial evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Methods Chemotherapy-naïve patients with advanced nsNSCLCs were treated with regorafenib 60mg/day continuously and cisplatin 75mg/m2 plus pemetrexed 500mg/m2 once every three weeks for up to six cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Results Nine patients enrolled prior to premature termination of the study due to slow recruitment and a change in the development strategy of regorafenib by the study sponsor, partially due to slow enrollment. Five patients experienced at least one treatment-related Grade 3 adverse event. No grade 4–5 toxicity occurred. 5 of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range 1.5–15.1). Minor pharmacokinetic (PK) interactions between regorafenib and chemotherapy were observed. Conclusions Regorafenib had acceptable tolerability and minor PK interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. Encouraging activity was appreciated in chemotherapy-naïve patients with advanced nsNSCLCs. However, the small number of patients treated limits conclusions that can be drawn from these results. PMID:26003007

  19. 125I brachytherapy of locally advanced non-small-cell lung cancer after one cycle of first-line chemotherapy:a comparison with best supportive care

    Directory of Open Access Journals (Sweden)

    Song J

    2017-03-01

    Full Text Available Jingjing Song* Xiaoxi Fan* Zhongwei Zhao* Minjiang Chen* Weiqian Chen, Fazong Wu, Dengke Zhang, Li Chen, Jianfei Tu, Jiansong Ji Department of Interventional Radiology, Zhejiang University Lishui Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, People’s Republic of China *These authors have contributed equally to this work Objectives: The objective of this study was to assess the efficacy of computed tomography (CT-guided 125I brachytherapy alone in improving the survival and quality of life of patients with unresectable locally advanced non-small-cell lung cancer (NSCLC after one cycle of first-line chemotherapy.Patients and methods: Sixteen patients with locally advanced NSCLC were treated with CT-guided 125I brachytherapy after one cycle of first-line chemotherapy (group A. Sixteen patients who received only best supportive care (group B were matched up with the patients in group A. Primary end point included survival, and secondary end point included assessment of safety, effectiveness of CT-guided 125I brachytherapy, and improvement in the quality of life.Results: The two groups were well balanced in terms of age, disease histology, tumor stage, tumor location, and performance status (P>0.05. The median follow-up time was 16 months (range, 3–30. The total tumor response rate was 75.0% in group A, which was significantly higher than that in group B (0.0% (P<0.01. The median progression-free survival time was 4.80 months for patients in group A and 1.35 months for patients in group B (P<0.001. Kaplan–Meier survival analysis showed that the median survival time of group A was 9.4±0.3 months versus 8.4±0.1 months in group B (P=0.013. Tumor-related symptoms of patients were significantly relieved, and the quality of life was markedly improved in group A than in group B.Conclusion: CT-guided 125I brachytherapy improved the survival of patients with locally advanced

  20. Comparison of Outcomes for Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Treated With Induction Chemotherapy Followed By Concurrent Chemoradiation vs. Concurrent Chemoradiation Alone

    International Nuclear Information System (INIS)

    Huang, Eugene H.; Liao Zhongxing; Cox, James D.; Guerrero, Thomas M.; Chang, Joe Y.; Jeter, Melinda; Borghero, Yerko; Wei Xiong; Fossella, Frank; Herbst, Roy S.; Blumenschein, George R.; Moran, Cesar; Allen, Pamela K.; Komaki, Ritsuko

    2007-01-01

    Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. Methods and Materials: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. Results: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p = 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40-0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p = 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28-0.78; p = 0.003). Conclusion: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung

  1. Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Ming Li

    Full Text Available To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC.A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS, progression-free survival (PFS, response rate (RR, and different types of toxicity. Hazard ratios (HRs, odds ratios (ORs and their 95% confidence intervals (CIs were pooled using RevMan software.Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC improved survival compared with other platinum-based regimens (PBR in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04, especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02. No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively. Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities.Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology.

  2. Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients

    Science.gov (United States)

    Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

    2016-01-01

    Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

  3. [The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

    Science.gov (United States)

    Chen, H; Wang, H P; Zhang, L; Si, X Y

    2017-01-01

    Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

  4. Changes in cross-sectional area of pulmonary vessels on chest computed tomography after chemotherapy in patients with advanced non-squamous non-small-cell lung cancer.

    Science.gov (United States)

    Karayama, Masato; Inui, Naoki; Kusagaya, Hideki; Suzuki, Seiichiro; Inoue, Yusuke; Enomoto, Noriyuki; Fujisawa, Tomoyuki; Nakamura, Yutaro; Suda, Takafumi

    2016-05-01

    Chemotherapy is associated with a risk of vascular damage. Novel anti-angiogenic agents, which can directly affect tumor angiogenesis, are increasingly being used. However, the effects of these agents on normal vasculature are not well understood. Here, we evaluated the effects of chemotherapy in general, and the anti-angiogenic agent bevacizumab, more specifically, on the pulmonary vasculature in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). For this, we used the cross-sectional area of pulmonary vessels (CSA), which is an easily measurable indicator of small pulmonary vasculature on non-contrast chest computed tomography (CT). We retrospectively reviewed CT scans of the lungs of 75 chemo-naïve patients with advanced non-squamous NSCLC, for measurement of CSA, before and after first-line platinum-based chemotherapy, using a semi-automatic image-processing program. Measured vessels were classified in two groups: small vessels with CSA area (%CSAsmall-diameter vessels, with a significant decrease in %CSAsmall pulmonary vascular damage. Use of bevacizumab does not enhance the reduction in area of pulmonary vessels.

  5. Is Huachansu Beneficial in Treating Advanced Non-Small-Cell Lung Cancer? Evidence from a Meta-Analysis of Its Efficacy Combined with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Bingduo Zhou

    2015-01-01

    Full Text Available Background. Huachansu, the sterilized water extract of Bufo bufo gargarizans toad skin, is used in China to alleviate the side-effects and enhance the therapeutic effect of chemotherapy in advanced non-small-cell lung cancer (NSCLC. We conducted a meta-analysis to assess Huachansu’s efficacy. Methods. We extensively searched electronic databases (CENTRAL, EMBASE, MEDLINE, CBM, Cochrane Library, CNKI, CEBM, WFDP, CSCD, CSTD, and IPA for randomized controlled trials containing Huachansu plus chemotherapy as the test group and chemotherapy as the control group. Seventeen trials were selected based on the selection criteria. The pooled relative ratio (RR of indicators with 95% confidence interval (95% CI was calculated for efficacy evaluation. Results. The meta-analysis demonstrated a statistically significant improvement in objective tumor response, one-year survival, Karnofsky performance status, pain relief, and alleviation of severe side-effects (nausea and vomiting, leukocytopenia in the test group as compared to the control group, but no significant difference in thrombocytopenia. Conclusions. This study demonstrated the efficacy of Huachansu combined with chemotherapy in the treatment of advanced NSCLC. However, limitations exist and high-quality trials are needed for further verification.

  6. Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

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    V. Surmont

    2009-01-01

    Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

  7. Efficacy and safety of iodine-125 radioactive seeds brachytherapy for advanced non-small cell lung cancer-A meta-analysis.

    Science.gov (United States)

    Zhang, Wenchao; Li, Jiawei; Li, Ran; Zhang, Ying; Han, Mingyong; Ma, Wei

    This meta-analysis was conducted to investigate the efficacy and safety of 125 I brachytherapy for locally advanced non-small cell lung cancer (NSCLC). Trials comparing 125 I brachytherapy with chemotherapy in NSCLC were identified. Meta-analysis was performed to obtain pooled risk ratios for an overall response rate (ORR), disease control rate (DCR) and complications, and pooled hazard ratio for overall survival (OS). Fifteen studies including 1188 cases were included. The pooled result indicated that there were significant differences in ORR, DCR, and OS between 125 I brachytherapy combined with chemotherapy and chemotherapy alone, but no statistic differences in gastrointestinal symptoms, leukopenia, myelosuppression, and hemoglobin reduction. Patients treated with 125 I brachytherapy combined with chemotherapy have a higher relative risk of pneumothorax, bloody sputum, and pneumorrhagia compared with chemotherapy alone. Seeds migration only occurred in the group treated with 125 I brachytherapy. There were significant differences in ORR, DCR, and myelosuppression between 125 I brachytherapy alone and chemotherapy. 125 I brachytherapy combined with chemotherapy can significantly enhance the clinical efficacy and improve the OS of patients with advanced NSCLC without increasing the incidence of complications of chemotherapy. 125 I brachytherapy alone can significantly enhance the clinical efficacy and reduce the incidence of myelosuppression compared with chemotherapy. However, 125 I brachytherapy may cause lung injury. Large sample and higher-quality randomized controlled trials are needed to confirm the pooled results of complications. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  8. Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

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    Necdet Uskent

    2017-10-01

    Full Text Available Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc. This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3rd, 6th, 9th, and 12th months of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.

  9. Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

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    Giroux Leprieur E

    2016-06-01

    Full Text Available Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy depends on the phenotype of the progression, the

  10. Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design.

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    Lal, Rohit; Bourayou, Nawel; Hillerdal, Gunnar; Nicolson, Marianne; Vikstrom, Anders; Lorenzo, Maria; D'yachkova, Yulia; Barriga, Susana; Visseren-Grul, Carla

    2013-10-03

    Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting. Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0-1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m(2) every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients' quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011. This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home-based chemotherapy. The study design

  11. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine.

    Science.gov (United States)

    Han, Yanxi; Li, Jinming

    2017-10-26

    In this era of precision medicine, molecular biology is becoming increasingly significant for the diagnosis and therapeutic management of non-small cell lung cancer. The specimen as the primary element of the whole testing flow is particularly important for maintaining the accuracy of gene alteration testing. Presently, the main sample types applied in routine diagnosis are tissue and cytology biopsies. Liquid biopsies are considered as the most promising alternatives when tissue and cytology samples are not available. Each sample type possesses its own strengths and weaknesses, pertaining to the disparity of sampling, preparation and preservation procedures, the heterogeneity of inter- or intratumors, the tumor cellularity (percentage and number of tumor cells) of specimens, etc., and none of them can individually be a "one size to fit all". Therefore, in this review, we summarized the strengths and weaknesses of different sample types that are widely used in clinical practice, offered solutions to reduce the negative impact of the samples and proposed an optimized strategy for choice of samples during the entire diagnostic course. We hope to provide valuable information to laboratories for choosing optimal clinical specimens to achieve comprehensive functional genomic landscapes and formulate individually tailored treatment plans for NSCLC patients that are in advanced stages.

  12. Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965).

    NARCIS (Netherlands)

    Dziadziuszko, R; Ardizzoni, A.; Postmus, P.E.; Smit, E.F.; Price, A; Debruyne, C.; Legrand, C; Giaccone, G.

    2003-01-01

    This study was performed to evaluate the activity of single-agent temozolomide in two groups of chemotherapy-naive non-small cell lung cancer (NSCLC) patients, with (12 patients) and without (13 patients) brain metastases (BM). Patients in both groups were treated with temozolomide 200 mg/m(2)/day,

  13. Erlotinib plus parenteral nutrition: an opportunity to get through the hardest days of advanced non-small cell lung cancer with cancer anorexia-cachexia syndrome.

    Science.gov (United States)

    Zang, Yuan-Sheng; Fang, Zheng; Li, Bing

    2013-03-01

    This case study details the poor performance status of a patient with non-small cell lung cancer and cancer anorexia-cachexia syndrome got through the hardest days of high tumor burden and malnutrition, by using a combined therapy of lung cancer-targeted therapy drug and parenteral nutrition. The related literatures were reviewed.

  14. Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer.

    Science.gov (United States)

    Socinski, Mark A; Govindan, Ramaswamy; Spigel, David

    2012-10-01

    Treatments for non-small cell lung cancer (NSCLC) are based on the broad categories of squamous or non-squamous histology. Frontline treatment options include pemetrexed and cisplatin, pemetrexed and a taxane, gemcitabine with cisplatin, and the addition of bevacizumab to a taxane and carboplatin. Pemetrexed is used for maintenance therapy for non-squamous NSCLC, whereas patients with squamous NSCLC lack easy options for maintenance therapy. nab-Paclitaxel overcomes the solubility and toxicity issues of solvent-based paclitaxel, and the albumin in nab-paclitaxel improves the concentration of the drug in the tumor. A recent phase III trial in NSCLC compared nab-paclitaxel with carboplatin versus solvent-based paclitaxel with carboplatin, and found improved overall response rates (ORRs) in the nab-paclitaxel arm (33% vs 25%; P=.005). In a subset analysis, NSCLC patients with squamous histology had a higher ORR (41%) with nab-paclitaxel than with solvent-based paclitaxel (24%; P<.001). Another subset analysis found that patients ages 70 years and older had improved overall survival (median 19.9 months) with nab-paclitaxel compared with solvent-based paclitaxel (median 10.4 months; P=.009). Patients in the nab-paclitaxel arm had less neuropathy, less hearing loss, and fewer interruptions in daily living than patients in the solvent-based paclitaxel arm.

  15. Preserving Functional Lung Using Perfusion Imaging and Intensity-Modulated Radiation Therapy for Advanced-Stage Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Shioyama, Yoshiyuki; Jang, Si Young; Liu, H. Helen; Guerrero, Thomas; Wang, Xuanmin; Gayed, Isis W.; Erwin, William D.; Liao, Zhongxing; Chang, Joe Y.; Jeter, Melenda; Yaremko, Brian P.; Borghero, Yerko O.; Cox, James D.; Komaki, Ritsuko; Mohan, Radhe

    2007-01-01

    Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients

  16. [Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

    Science.gov (United States)

    Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

    2015-06-01

    This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

  17. Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shuyang YAO

    2015-06-01

    Full Text Available Background and objective This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed in previously treated advanced non-small cell lung cancer (NSCLC. Methods Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS was evaluated by Kaplan-Meier method. Results Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR (28.1% vs 18.2%, P=0.341, disease control rate (DFS(43.8% vs 45.5%, P=0.890, and PFS (4.3 months vs 3.8 months, P=0.506. In the icotinib group, the ORR of epidermal growth factor receptor (EGFR mutant was significantly higher than that of EGFR unknown or wild type (P=0.017. In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001. Conclusion Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

  18. Analysis of Differentially Expressed Proteins in Self-Paired Sera of Advanced Non-small Cell Lung Cancer Patients Responsive to Gefin

    Directory of Open Access Journals (Sweden)

    Ying HUANG

    2009-07-01

    Full Text Available Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy. The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor (EGFR tyrosine kinase inhibitor (TKI targeted therapy in advanced non-small cell lung cancer. Methods Twenty self-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control (SD or PR after gefinitib therapy, at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress. All samples were pre-separated by WCX microbeads, and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM. ClinProTools (Version: 2.1 was used to analyze the differentially expressed proteins. Results There were 7 protein peaks (m/z, 3242.09, 8 690.36, 2 952.64, 3 224.04, 1 450.51, 1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples. Three proteins (3 242.09, 2 952.64 and 3 224.04 were down-regulated and four proteins (8 690.36, 1 450.51, 1 887.8 and 3 935.73 up-regulated in gefinitib treated sera. Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance, yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation.

  19. Evaluation of a prognostic scoring system based on the systemic inflammatory and nutritional status of patients with locally advanced non-small-cell lung cancer treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Mitsuyoshi, Takamasa; Matsuo, Yukinori; Itou, Hitoshi; Shintani, Takashi; Iizuka, Yusuke; Kim, Young Hak; Mizowaki, Takashi

    2018-01-01

    Systemic inflammation and poor nutritional status have a negative effect on the outcomes of cancer. Here, we analyzed the effects of the pretreatment inflammatory and nutritional status on clinical outcomes of locally advanced non-small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy. We retrospectively reviewed 89 patients with locally advanced NSCLC treated with chemoradiotherapy between July 2006 and June 2013. Serum C-reactive protein (CRP) was assessed as an inflammatory marker, and serum albumin, body mass index (BMI) and skeletal mass index were assessed as nutritional status markers. The relationships between these markers and overall survival (OS) were assessed. The median OS was 24.6 months [95% confidence interval (CI): 19.4–39.3 months]. During follow-up, 58 patients (65%) had disease recurrence and 52 patients (58%) died. In multivariate Cox hazard analysis, CRP levels and BMI approached but did not achieve a significant association with OS (P = 0.062 and 0.094, respectively). Recursive partitioning analysis identified three prognostic groups based on hazard similarity (CRP-BMI scores): 0 = CRP < 0.3 mg/dl, 1 = CRP ≥ 0.3 mg/dl and BMI ≥ 18.5 kg/m 2 , and 2 = CRP ≥ 0.3 mg/dl and BMI < 18.5 kg/m 2 . The CRP-BMI score was significantly associated with OS (P = 0.023). Patients with scores of 0, 1 and 2 had median OS of 39.3, 24.5 and 14.5 months, respectively, and the scores also predicted the probability of receiving salvage treatment after recurrence. The CRP-BMI score is thus a simple and useful prognostic marker of clinical outcome for patients with locally advanced NSCLC treated with chemoradiotherapy.

  20. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    International Nuclear Information System (INIS)

    Zhu, Jun; Li, Te; Wang, Xiaohui; Ye, Ming; Cai, Jian; Xu, Yuejuan; Wu, Bin

    2013-01-01

    Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated. After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option

  1. Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.

    Science.gov (United States)

    Zhang, Wenxiong; Wei, Yiping; Yu, Dongliang; Xu, Jianjun; Peng, Jinhua

    2018-04-01

    The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed. Forty studies comprising 9376 participants were included. The results suggested that gefitinib and erlotinib are effective for advanced NSCLC with comparable PFS (95% confidence intervals [CI]: 0.98-1.11, P = .15), OS (95% CI: 0.93-1.19, P = .45), ORR (95% CI: 0.99-1.16, P = .07), and DCR (95% CI: 0.92-1.03, P = .35). For erlotinib, dose reduction was significantly more frequent (95% CI: 0.10-0.57, P = .001) as were grade 3 to 5 AEs (95% CI: 0.36-0.79, P = .002). In the subgroup analysis, the erlotinib group had a significant higher rate and severity of skin rash, nausea/vomiting, fatigue, and stomatitis. Gefitinib was proven to be the better choice for advanced NSCLC, with equal antitumor effectiveness and fewer AEs compared with erlotinib. Further large-scale, well-designed randomized controlled trials are warranted to confirm our validation.

  2. Quality of life, symptom status and physical performance in patients with advanced non-small cell lung cancer undergoing chemotherapy: an exploratory analysis of secondary data.

    Science.gov (United States)

    Shallwani, Shirin M; Simmonds, Maureen J; Kasymjanova, Goulnar; Spahija, Jadranka

    2016-09-01

    Our objectives were: (a) to identify predictors of change in health-related quality of life (HRQOL) in patients with advanced non-small cell lung cancer (NSCLC) undergoing chemotherapy; and (b) to characterize symptom status, nutritional status, physical performance and HRQOL in this population and to estimate the extent to which these variables change following two cycles of chemotherapy. A secondary analysis of a longitudinal observational study of 47 patients (24 men and 23 women) with newly diagnosed advanced NSCLC receiving two cycles of first-line chemotherapy was performed. Primary outcomes were changes in HRQOL (physical and mental component summaries (PCS and MCS) of the 36-item Short-Form Health Survey (SF-36)). Predictors in the models included pre-chemotherapy patient-reported symptoms (Schwartz Cancer Fatigue Scale (SCFS) and Lung Cancer Subscale), nutritional screening (Patient-Generated Subjective Global Assessment) and physical performance measures (6-min Walk Test (6MWT), one-minute chair rise test and grip strength). Mean SF-36 PCS score, 6MWT distance and grip strength declined following two cycles of chemotherapy (pmental component of HRQOL accounting for 13% and 9% of the variance, respectively. No significant predictors were found for change in the physical component of HRQOL. Pre-chemotherapy 6MWT distance and fatigue severity predicted change in the mental component of HRQOL in patients with advanced NSCLC undergoing chemotherapy, while physical performance declined during treatment. Clinical management of these factors may be useful for HRQOL optimization in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Treatment adherence in concurrent chemoradiation in patients with locally advanced non-small cell lung carcinoma: Results of daily intravenous prehydration

    International Nuclear Information System (INIS)

    Uyterlinde, Wilma; Chen, Chun; Nijkamp, Jasper; Obbink, Marieke Groot; Sonke, Jan-Jakob; Belderbos, Jose; Heuvel, Michel van den

    2014-01-01

    Purpose: To test the hypothesis that daily intravenous pre-hydration decreases renal toxicity and improves chemotherapy adherence in patients receiving daily cisplatin to concurrent radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with locally advanced NSCLC were treated between 2008 and August 2012 with daily 6 mg/m 2 cisplatin as a bolus injection in 10 ml; of saline and 66 Gy/24 fr radiotherapy in 32 days. Since January 2011, the administration of cisplatin was routinely preceded by intravenous pre-hydration with 1 L of natriumchloride 0.9%. Patients were divided in a pre-hydrated (PH) and non-pre-hydrated (NPH) cohort. Serum-creatinine and glomerular filtration rate (GFR) were assessed twice weekly during treatment. Retrospectively, baseline data, toxicity, treatment adherence and efficacy data were compared. Results: Of the 356 patients 232 NPH patients and 100 PH patients were eligible. Patient-and treatment characteristics compared equally. The median of the maximum decrease in GFR was 24% and 8% for NPH and PH (p < 0.01), respectively. Sixty-nine percent of the patients in the NPH group completed the 24 administrations of cisplatin, as compared to 83% of the PH group (p < 0.01). Nineteen percent vs. 2% of the patients in the NPH and PH group discontinued cisplatin treatment because of renal toxicity. Surprisingly, the incidence of acute esophageal toxicity grade ⩾2 decreased following prehydration: 62% vs. 34% (p < 0.001) for the NPH and PH groups, respectively. The one-year survival was comparable between groups (75% for NPH and 71% for PH). Conclusion: Daily pre-hydration was associated with a reduced rate of both renal and acute esophageal toxicity and an increased chemotherapy adherence in patients receiving daily dose of cisplatin and concurrent radiotherapy for locally advanced NSCLC

  4. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Li-li ZHANG

    2013-09-01

    Full Text Available Objective To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

  5. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    Directory of Open Access Journals (Sweden)

    Zhu Jun

    2013-01-01

    Full Text Available Abstract Background Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. Methods A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER at a willingness-to-pay (WTP threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP was evaluated. Results After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP. The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. Conclusions These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.

  6. Maintenance treatment of advanced non-small-cell lung cancer: results of an international expert panel meeting of the Italian association of thoracic oncology.

    Science.gov (United States)

    Gridelli, Cesare; de Marinis, Filippo; Di Maio, Massimo; Ardizzoni, Andrea; Belani, Chandra P; Cappuzzo, Federico; Ciardiello, Fortunato; Fidias, Panagiotis; Paz-Ares, Luis; Perrone, Francesco; Pirker, Robert; De Petris, Luigi; Stahel, Rolf

    2012-06-01

    Several randomized trials have recently investigated the role of maintenance treatment for patients with advanced non-small-cell lung cancer (NSCLC) with responding or stable disease after completion of first-line chemotherapy. Maintenance strategy has relevant implications in terms of potential toxicity, logistics and costs, and all of these aspects should be taken into account, together with the magnitude of benefit for the patient. In order to assess the strengths and limitations of available evidence, to help clinical practice, and to suggest priorities for future clinical research, the Italian Association of Thoracic Oncology (AIOT) organized an International Experts Panel Meeting on maintenance treatment of advanced NSCLC, which took place in Sperlonga (Italy) in May 2011. Based on the available evidence, panelists agreed that maintenance therapy represents a treatment option in advanced NSCLC. Maintenance should be discussed with patients not progressed after 4-6 cycles of first-line chemotherapy, who are fit (performance status 0-1) and without persistent chemotherapy-induced toxicity. Patients need to be well informed about potential advantages and disadvantages of accepting additional therapy without a "treatment-free period". Two different strategies, switch or continuation maintenance, are supported by available evidence. At the moment, there is no direct comparison between switch maintenance and continuation maintenance. For future trials, the panel recommends the use of overall survival as the primary endpoint, with pre-defined second-line treatment. Translational research is essential to identify predictive factors, and should be performed, whenever feasible, in order to achieve treatment optimization with proper patient selection. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH)

    NARCIS (Netherlands)

    Peters, S.; Gettinger, S.; Johnson, M.L.; Janne, P.A.; Garassino, M.C.; Christoph, D.; Toh, C.K.; Rizvi, N.A.; Chaft, J.E.; Costa, E.; Patel, J.D.; Chow, L.Q.M.; Koczywas, M.; Ho, C.; Fruh, M.; Heuvel, M. van den; Rothenstein, J.; Reck, M.; Paz-Ares, L.; Shepherd, F.A.; Kurata, T.; Li, Z.; Qiu, J.; Kowanetz, M.; Mocci, S.; Shankar, G.; Sandler, A.; Felip, E.

    2017-01-01

    Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or

  8. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

    Science.gov (United States)

    Liang, Wenhua; Wu, Xuan; Fang, Wenfeng; Zhao, Yuanyuan; Yang, Yunpeng; Hu, Zhihuang; Xue, Cong; Zhang, Jing; Zhang, Jianwei; Ma, Yuxiang; Zhou, Ting; Yan, Yue; Hou, Xue; Qin, Tao; Dinglin, Xiaoxiao; Tian, Ying; Huang, Peiyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2014-01-01

    Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons. We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR), progression free survival (PFS), overall survival (OS) were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs) based on Bayesian network integrated the efficacy and specific toxicities of all included treatments. Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, Picotinib (19%, 29%, NA, NA), respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib. The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed potentially better efficacy but significant higher toxicities compared with gefitinib and icotinib.

  9. Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

    Science.gov (United States)

    Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

    2017-02-07

    Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

  10. Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature.

    Science.gov (United States)

    Singh, Navneet; Jindal, Aditya; Behera, Digambar

    2014-12-10

    Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer (NSCLC). They are both tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female (60.6%), non-smokers (64.5%), had adenocarcinoma histology (88.3%) and were of East Asian ethnicity (92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanisms especially those related to resistance to initial EGFR TKI therapy.

  11. The correlation between clinical factors and radiation pneumonitis in advanced stage non-small-cell lung cancer treated with concurrent radiochemotherapy

    International Nuclear Information System (INIS)

    Han Lei; Lu Bing; Fu Heyi; Hu Yinxiang; Gan Jiaying; Li Huiqin

    2011-01-01

    Objective: To evaluate clinical factors as predictors of radiation pneumonitis (RP)in advanced stage non-small cell lung cancer (NSCLC) patients treated with concurrent radio chemotherapy when gross tumor volume is 70 Gy. Methods: Data of 84 patients with histologically proved NSCLC treated with 3DCRT or IMRT were collected. To evaluate the correlation between clinical parameters and radiation pneumonitis (RP). The clinical parameters were considered: pathological type, therapy agents, age,gender, stage, karnofsky performance status (KPS), smoking status, diabetes, chronic obstructive pulmonary disease (COPD). Results: The occurrence of grade 1, 2 RP was 63%, 33%, respectively. In univariate analysis, diabetes was significantly associated with RP of ≥ grade 1(χ 2 =4.03, P = 0.045)and ≥grade 2(χ 2 = 15.59, P =0.000). KPS was significantly associated with RP of ≥grade 1(χ 2 =3.98, P = 0.046)and ≥grade 2(χ 2 = 5.21, P = 0.023). In logistic multivariate analysis, diabetes was significantly associated with RP of ≥grade 1(χ 2 =5.50, P =0.019)and ≥grade 2(χ 2 = 12.92, P =0.000). KPS was significantly associated with RP of ≥ grade 1(χ 2 = 6.29, P = 0.012)and ≥ grade 2(χ 2 = 6.61, P =0.010). Conclusion: The definite statistical significant risk factors of RP are diabetes and KPS. (authors)

  12. Multidisciplinary team approach for the management of patients with locally advanced non-small cell lung cancer: Searching the evidence to guide the decision

    International Nuclear Information System (INIS)

    Oh, In Jae; Ahn, Sung Ja

    2017-01-01

    Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article

  13. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    International Nuclear Information System (INIS)

    Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

    2012-01-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior–posterior), and z (superior–inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy–based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

  14. Multidisciplinary team approach for the management of patients with locally advanced non-small cell lung cancer: Searching the evidence to guide the decision

    Energy Technology Data Exchange (ETDEWEB)

    Oh, In Jae; Ahn, Sung Ja [Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

    2017-03-15

    Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article.

  15. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Roman, Nicholas O., E-mail: nroman@mcvh-vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Shepherd, Wes [Department of Pulmonology, Virginia Commonwealth University, Richmond, VA (United States); Mukhopadhyay, Nitai [Department of Biostatistics, Virginia Commonwealth University, Richmond, VA (United States); Hugo, Geoffrey D.; Weiss, Elisabeth [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

    2012-08-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

  16. Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer.

    Science.gov (United States)

    Mellema, Wouter W; Masen-Poos, Lucie; Smit, Egbert F; Hendriks, Lizza E L; Aerts, Joachim G; Termeer, Arien; Goosens, Martijn J; Smit, Hans J M; van den Heuvel, Michel M; van der Wekken, Anthonie J; Herder, Gerarda J M; Krouwels, Frans H; Stigt, Jos A; van den Borne, Ben E E M; Haitjema, Tjeerd J; Staal-Van den Brekel, Agnes J; van Heemst, Robbert C; Pouw, Ellen; Dingemans, Anne-Marie C

    2015-11-01

    As suggested by in-vitro data, we hypothesize that subtypes of KRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinum-based chemotherapy, were retrieved from hospital databases. to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation. 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of KRAS mutation were G12C (46%), G12V (20%) and G12D (10%). Platinum was combined with pemetrexed (n=334), taxanes (n=68) or gemcitabine (n=62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; pchemotherapy had best ORR. Response to chemotherapy regimens was different in types of KRAS mutation. Especially patients with G12V had better response to taxane treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Quality of life assessment in advanced non-small-cell lung cancer patients undergoing an accelerated radiotherapy regimen: report of ECOG study 4593

    International Nuclear Information System (INIS)

    Auchter, Richard M.; Scholtens, Denise; Adak, Sudeshna; Wagner, Henry; Cella, David F.; Mehta, Minesh P.

    2001-01-01

    Purpose: To prospectively evaluate the quality of life (QOL) before, at completion, and after therapy for patients receiving an accelerated fractionation schedule of radiotherapy for advanced, unresectable non-small-cell lung cancer in a Phase II multi-institutional trial. Methods and Materials: The Functional Assessment of Cancer Therapy-Lung (FACT-L) patient questionnaire was used to score the QOL in patients enrolled in the Eastern Cooperative Oncology Group Phase II trial (ECOG 4593) of hyperfractionated accelerated radiotherapy in non-small-cell lung cancer. Radiotherapy (total dose 57.6 Gy in 36 fractions) was delivered during 15 days, with three radiation fractions given each treatment day. The protocol was activated in 1993, and 30 patients had accrued by November 1995. The FACT-L questionnaire was administered at study entry (baseline), on the last day of radiotherapy (assessment 2), and 4 weeks after therapy (assessment 3). The FACT-L includes scores for physical, functional, emotional, and social well-being (33 items), and a subscale of lung cancer symptoms (10 additional items). The summation of the physical, functional, and lung cancer symptom subscales (21 items) constitutes the Trial Outcome Index (TOI), considered the most clinically relevant outcome measure in lung cancer treatment trials. Results: The FACT-L completion rates at the designated study time points were as follows: baseline, 30 of 30 (100%); assessment 2, 29 (97%) of 30; and assessment 3, 24 (80%) of 30. At treatment completion, statistically significant declines in QOL scores were noted, compared with baseline for physical and functional well-being. Emotional well-being scores improved at both assessment 2 and assessment 3. The physical and functional scores returned approximately to baseline values at assessment 3. The change in TOI score was evaluated as a function of the clinical response to treatment, toxicity grade, and survival; no clear association was noted. A trend for the

  18. Correlations between Ape1/Ref-1, ICAM-1 and IL-17A Levels in Serum and Radiation Pneumonitis for Local Advanced Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Leiming GUO

    2018-05-01

    Full Text Available Background and objective The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1, intercellular adhesion molecules 1 (ICAM-1 and interleukin-17A (IL-17A before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC patients with concurrent chemoradiotherapy. Methods NSCLC patients (68 cases were treated with concurrent radiotherapy and chemotherapy, every patient’s normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. Results Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05. There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05. Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in

  19. Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes

    International Nuclear Information System (INIS)

    Fernandes, Annemarie T.; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

    2010-01-01

    Background: Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. Methods: We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Results: Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Conclusions: Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.

  20. Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes.

    Science.gov (United States)

    Fernandes, Annemarie T; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

    2010-05-01

    Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  2. Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Trinkaus, Mateya E.; Rischin, Danny; Blum, Rob

    2013-01-01

    For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ( 18 F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Patients with stage IIIA-IIIB NSCLC underwent 18 F-FAZA PET scans and 18 F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). Seventeen patients underwent pre-treatment 18 F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P=0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P=0.38). Eight patients with baseline hypoxia had post treatment 18 F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P=0.42). Intra-lesional hypoxia, as detected by 18 F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.

  3. Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer.

    Science.gov (United States)

    Imai, Hisao; Kuwako, Tomohito; Kaira, Kyoichi; Masuda, Tomomi; Miura, Yosuke; Seki, Kaori; Sakurai, Reiko; Utsugi, Mitsuyoshi; Shimizu, Kimihiro; Sunaga, Noriaki; Tomizawa, Yoshio; Ishihara, Shinichi; Ishizuka, Takao; Mogi, Akira; Hisada, Takeshi; Minato, Koichi; Takise, Atsushi; Saito, Ryusei; Yamada, Masanobu

    2017-03-01

    In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients. The medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed. The median BSA and BW were used as cutoff values to evaluate their impact on gefitinib efficacy. BMI was categorized as underweight (<18.5 kg/m 2 ), normal (18.5-25 kg/m 2 ), and overweight (≥25 kg/m 2 ). The median BSA and BW were 1.48 m 2 and 53 kg, respectively. The overall response rate, progression-free survival (PFS), and overall survival (OS) were 65.2%, 12.2, and 24.2 months, respectively. There were no significant differences in clinical outcomes according to BSA, BW, or BMI alone. Subgroup analysis based on the mutation type and BSA revealed no significant differences in PFS between the groups; however, the median OS in those with exon 19 deletion combined with low BSA was significantly favorable compared with the other groups. Gefitinib efficacy in patients with NSCLC harboring sensitive EGFR mutations did not differ according to BSA, BW, and BMI. However, OS was superior in patients with both the exon 19 deletion and low BSA.

  4. Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer. A phase I study

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    Gagel, B.; Piroth, M.; Pinkawa, M.; Fischedik, K.; Asadpour, B.; Schmachtenberg, A.; Eble, M.J. [Dept. of Radiotherapy, RWTH Aachen (Germany); Reinartz, P.; Zimny, M.; Buell, U. [Dept. of Nuclear Medicine, RWTH Aachen (Germany); Stanzel, S. [Inst. for Medical Statistics, RWTH Aachen (Germany); Breuer, C.; Skobel, E. [Dept. of Internal Medicine I, RWTH Aachen (Germany)

    2006-05-15

    Purpose: to determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). Patients and methods: ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m{sup 2}) and vinorelbine (30 mg/m{sup 2}) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [{sup 18}F] fluorodeoxyglucose positron emission tomography-(FDG-PET-) based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m{sup 2}. The dose of gemcitabine was increased by 100 mg/m{sup 2} until the MTD was realized. Three patients were enrolled for each dose level. Results: dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m{sup 2}, due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. Conclusion: after induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m{sup 2} every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy. (orig.)

  5. Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

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    West, Howard

    2017-09-01

    The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor ( EGFR ) mutation or an anaplastic lymphoma kinase ( ALK ) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

  6. Assessing functional status and the survival benefit of chemotherapy for advanced non-small cell lung cancer using administrative claims data.

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    Feliciano, Josephine; Gardner, Lisa; Hendrick, Franklin; Edelman, Martin J; Davidoff, Amy

    2015-01-01

    Borderline or poor performance status (PS) patients comprise a significant proportion of those diagnosed with advanced non-small cell lung cancer (AdvNSCLC), but are often excluded from clinical trials. It is difficult to draw conclusions about the benefit of therapy in borderline PS patients due to lack of reliable PS assessments, and small clinical trial samples. Retrospective population-based secondary analyses may allow investigators to study under-represented populations in clinical trials. We hypothesized that patients with poor functional status derive benefit from chemotherapy compared good functional status, but that the magnitude of the benefit is lower compared to patients with good functional status. By utilizing a "disability status" (DS) measure as a proxy for PS, we offer a reliable mechanism for patient stratification that can be implemented in administrative claims data. Medicare beneficiaries diagnosed with AdvNSCLC between 2001 and 2005 were selected from the Surveillance, Epidemiology and End Results database linked to Medicare claims. Disability status, a previously developed and validated claims-based proxy for baseline PS, was implemented. Patients were assigned to good versus poor DS. Cox proportional hazard models were used to examine the differential effects of chemotherapy for the two DS groups on all-cause mortality, controlling for tumor and patient characteristics. Most patients in the cohort (n=21,019) were ≥75 years of age (59%), and non-Hispanic white (85%); 91% were assigned to good DS; 38% received chemotherapy. Chemotherapy had a strong protective effect among good DS patients (hazard ratio, 0.43; CI 0.42-0.45; pChemotherapy improves survival for advanced NSCLC patients with poor DS but to a lower magnitude than for good DS patients. The DS measure opens the door to assess outcomes for cancer patients with poor functional status using insurance claims data. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

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    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  8. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    Directory of Open Access Journals (Sweden)

    Chunxiang Zhang

    Full Text Available Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC from the perspective of the Chinese healthcare system.Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs and incremental cost-utility ratios (ICURs were calculated. One-way and probabilistic sensitivity analyses (PSA were performed.Our model suggested that the median progression-free survival (PFS was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  9. Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Shen, Xinglei; DeNittis, Albert; Werner-Wasik, Maria; Axelrod, Rita; Gilman, Paul; Meyer, Thomas; Treat, Joseph; Curran, Walter J; Machtay, Mitchell

    2011-01-01

    This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m 2 . Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m 2 , but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m 2 ) q3 weeks × 2 -3 cycles. Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m 2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.

  10. Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Treat Joseph

    2011-02-01

    Full Text Available Abstract Background This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week pemetrexed given concurrently with radiotherapy (XRT for locally advanced and oligometastatic non-small cell lung cancer (NSCLC. Methods Eligible patients had Stage III or IV (oligometastatic NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6 during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1 of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT in dose level 1, an amended dose level (level 1A continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6 and pemetrexed (500 mg/m2 q3 weeks × 2 -3 cycles. Results Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis. There was one DLT (grade 5 pneumonitis in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease, the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated in stage III patients. Conclusions Concurrent carboplatin with dose-dense (q2week pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC. Trial Registration ClinicalTrials.gov NCT00330044

  11. Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

    2015-05-15

    Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

  12. Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study.

    Science.gov (United States)

    Lee, Dae Ho; Isobe, Hiroshi; Wirtz, Hubert; Aleixo, Sabina Bandeira; Parente, Phillip; de Marinis, Filippo; Huang, Min; Arunachalam, Ashwini; Kothari, Smita; Cao, Xiting; Donnini, Nello; Woodgate, Ann-Marie; de Castro, Javier

    2018-03-01

    Data are scarce regarding real-world health care resource use (HCRU) for non-small cell lung cancer (NSCLC). An understanding of current clinical practices and HCRU is needed to provide a benchmark for rapidly evolving NSCLC management recommendations and therapeutic options. The objective of this study was to describe real-world HCRU for patients with advanced NSCLC. This multinational, retrospective chart review study was conducted at academic and community oncology sites in Italy, Spain, Germany, Australia, Japan, South Korea, Taiwan, and Brazil. Deidentified data were drawn from medical records of 1440 adults (≥18 years old) who initiated systemic therapy (2011 to mid-2013) for a new, confirmed diagnosis of advanced or metastatic (stage IIIB or IV) NSCLC. We summarized HCRU associated with first and subsequent lines of systemic therapy for advanced/metastatic NSCLC. The proportion of patients who were hospitalized at least once varied by country from 24% in Italy to 81% in Japan during first-line therapy and from 22% in Italy to 84% in Japan during second-line therapy; overall hospitalization frequency was 2.5-11.1 per 100 patient-weeks, depending on country. Emergency visit frequency also varied among countries (overall from 0.3-5.9 per 100 patient-weeks), increasing consistently from first- through third-line therapy in each country. The outpatient setting was the most common setting of resource use. Most patients in the study had multiple outpatient visits in association with each line of therapy (overall from 21.1 to 59.0 outpatient visits per 100 patient-weeks, depending on country). The use of health care resources showed no regular pattern associated with results of tests for activating mutations of the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. HCRU varied across countries. These findings suggest differing approaches to the clinical management of advanced NSCLC among the eight countries

  13. Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review

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    Zhang D

    2016-06-01

    Full Text Available Dianbao Zhang,1,* Xianfen Zhang,2,* Chunling Zhao1 1Department of Medical Oncology, 2Department of Cardiac Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, People’s Republic of China *These authors contributed equally to this work Aims: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs associated with antivascular endothelial growth factor (VEGF agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC patients. Methods: We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR, and 95% confidence intervals (CIs were pooled according to the heterogeneity of included trials. Results: A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00–2.07, P=0.048, but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56–1.59, P=0.82 compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67–1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73–1.22, P=0.67, respectively was observed in advanced NSCLC patients receiving anti-VEGF agents. Conclusion: The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients. Keywords: anti-VEGF agents, toxicity, arterial thromboembolic events, venous thromboembolic events, meta-analysis

  14. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

    International Nuclear Information System (INIS)

    Zhao, Jun; Zheng, Shuang; Zhou, Qiyin; Li, Heming; Liu, Yunpeng; Qu, Xiujuan; Zhao, Mingfang; Jin, Bo; Yu, Ping; Hu, Xuejun; Teng, Yuee; Zhang, Jingdong; Luo, Ying; Zhang, Lingyun

    2012-01-01

    Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. This study showed that the reduction in plasma fibrinogen levels

  15. Definitive Radiotherapy of Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lee, Jong Young; Park, Kyung Ran

    1995-01-01

    Purpose : The effect of dose escalation of up to 6500 cGy on local control and survival was investigated in locally advanced non-small cell lung cancer. Materials and Methods : Ninety eight patients with biopsy-proven unresectable non-small cell lung cancer without distant metastases or medically inoperable patients with lower-stage were treated with definitive radiotherapy alone. Group A were treated by thoracic irradiation, 6000 cGy or less in total tumor dose with daily fractions of 180 to 200 cGy: and group B was treated with 6500 cGy of same daily fractions. Results : The actuarial overall survival rate for the entire group was 54% at 1 year, 26.6% at 2 years and 16.4% at 3 years with a median survival time of 13 months. Statistically significant prognostic factors that affect survival rate were stage and N-stage. However, no improvement in local control and survival has been seen with higher dose radiotherapy(group B). Conclusion : Dose escalation of up to 6500 cGy was no effect on local control and survival rate. To increase the survival rate of non-small cell lung cancer hyperfractionated radiotherapy or concurrent chemoradiotherapy should be considered

  16. EGFR mutation testing in patients with advanced non-small cell lung cancer: a comprehensive evaluation of real-world practice in an East Asian tertiary hospital.

    Science.gov (United States)

    Choi, Yoon-La; Sun, Jong-Mu; Cho, Juhee; Rampal, Sanjay; Han, Joungho; Parasuraman, Bhash; Guallar, Eliseo; Lee, Genehee; Lee, Jeeyun; Shim, Young Mog

    2013-01-01

    Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (Pwomen, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.

  17. Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-05-01

    Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

  18. Overexpression of EMMPRIN is associated with lymph node metastasis and advanced stage of non-small cell lung cancer: a retrospective study

    OpenAIRE

    Liu, Bing; Wan, Zhaohui; Sheng, Baowei; Lin, Yong; Fu, Tian; Zeng, Qingdi; Qi, Congcong

    2017-01-01

    Background Previous studies show that overexpression of EMMPRIN involved in the malignant biological behavior of tumors. This investigation was to disclose the expression status of EMMPRIN in non-small cell lung cancer (NSCLC) and its clinical value for the diagnosis of NSCLC. Methods The expression of EMMPRIN was examined using immunohistochemistry and enzyme-linked immunosorbent assay. The clinical value of EMMPRIN was evaluated by drawing a receiver operating characteristic (ROC) curve. Re...

  19. Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

    Science.gov (United States)

    Srdic, Drazena; Plestina, Sanja; Sverko-Peternac, Ana; Nikolac, Nora; Simundic, Ana-Maria; Samarzija, Miroslav

    2016-11-01

    Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients

  20. {sup 18}F-alfatide PET/CT may predict short-term outcome of concurrent chemoradiotherapy in patients with advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Luan, Xiaohui [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China); University of Jinan-Shandong Academy of Medical Sciences, School of Medicine and Life Sciences, Jinan (China); Huang, Yong; Sun, Xiaorong; Ma, Li; Teng, Xuepeng; Lu, Hong [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiology, Jinan, Shandong (China); Gao, Song [Jining Infectious Diseases Hospital, Department of Oncology, Jining, Shandong (China); Wang, Suzhen; Yu, Jinming; Yuan, Shuanghu [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China)

    2016-12-15

    The study aims to investigate the role of {sup 18}F-alfatide positron emission tomography/computed tomography (PET/CT) in predicting the short-term outcome of concurrent chemoradiotherapy (CCRT) in patients with advanced non-small cell lung cancer (NSCLC). Eighteen patients with advanced NSCLC had undergone {sup 18}F-alfatide PET/CT scans before CCRT and PET/CT parameters including maximum and mean standard uptake values (SUV{sub max}/SUV{sub mean}), peak standard uptake values (SUV{sub peak}) and tumor volume (TV{sub PET} and TV{sub CT}) were obtained. The SUV{sub max} of tumor and normal tissues (lung, blood pool and muscle) were measured, and their ratios were denoted as T/NT (T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle}). Statistical methods included the Two-example t test, Wilcoxon rank-sum test, Receiver-operating characteristic (ROC) curve analysis and logistic regression analyses. We found that SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were higher in non-responders than in responders (P = 0.0024, P = 0.016, P < 0.001, P = 0.003, P = 0.004). According to ROC curve analysis, the thresholds of SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were 5.65, 4.46, 7.11, 5.41, and 11.75, respectively. The five parameters had high sensitivity, specificity and accuracy in distinguishing non-responders and responders. Multivariate logistic regression analyses showed that T/NT{sub lung} was an independent predictor of the short-term outcome of CCRT in patients with advanced NSCLC (P = 0.032). {sup 18}F-alfatide PET/CT may be useful in predicting the short-term outcome of CCRT in patients with advanced NSCLC. (orig.)

  1. Pemetrexed plus carboplatin versus pemetrexed in pretreated patients with advanced non-squamous non-small-cell lung cancer : treating the right patients based on individualized treatment effect prediction

    NARCIS (Netherlands)

    van Kruijsdijk, R. C. M.; Visseren, F. L. J.; Boni, L.; Groen, H. J. M.; Dingemans, A. M. C.; Aerts, J. G. J. V.; van der Graaf, Y.; Ardizzoni, A.; Smit, E. F.

    In this study, it is shown that there is important heterogeneity in the effects of pemetrexed-carboplatin versus pemetrexed on progression-free survival in pretreated patients with advanced non-squamous non-small-cell lung cancer. Treatment effect can be predicted for individual patients using a

  2. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  3. Efficacy and safety of COX-2 inhibitors for advanced non-small-cell lung cancer with chemotherapy: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Dai P

    2018-02-01

    Full Text Available Ping Dai, Jing Li, Xiao-Ping Ma, Jian Huang, Juan-Juan Meng, Ping Gong Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China Background: The study of cyclooxygenase-2 (COX-2 inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0.Results: Six eligible trials (1,794 patients were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06–1.48. Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib and treatment line (first or second chemotherapy. The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin, GP (double fluorine cytidine + cisplatin or carboplatin, or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin. The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08–2.25 and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07–1.50. However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91–1

  4. Predictors of grade {>=}2 and grade {>=}3 radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dang, Jun; Li, Guang; Ma, Lianghua; Han, Chong; Zhang, Shuo; Yao, Lei [Dept. of Radiation Oncology, The First Hospital of China Medical Univ., Shenyang (China)], e-mail: gl1963516@yahoo.cn; Diao, Rao [Dept. of Experimental Technology Center, China Medical Univ., Shenyang (China); Zang, Shuang [Dept. of Nursing, China Medical Univ., Shenyang (China)

    2013-08-15

    Grade {>=}3 radiation pneumonitis (RP) is generally severe and life-threatening. Predictors of grade {>=}2 are usually used for grade {>=}3 RP prediction, but it is unclear whether these predictors are appropriate. In this study, predictors of grade {>=}2 and grade {>=}3 RP were investigated separately. The increased risk of severe RP in elderly patients compared with younger patients was also evaluated. Material and methods: A total of 176 consecutive patients with locally advanced non-small cell lung cancer were followed up prospectively after three-dimensional conformal radiotherapy. RP was graded according to Common Terminology Criteria for Adverse Events version 3.0. Results: Mean lung dose (MLD), mean heart dose, ratio of planning target volume to total lung volume (PTV/Lung), and dose-volume histogram comprehensive value of both heart and lung were associated with both grade {>=}2 and grade {>=}3 RP in univariate analysis. In multivariate logistic regression analysis, age and MLD were predictors of both grade {>=}2 RP and grade {>=}3 RP; receipt of chemotherapy predicted grade {>=}3 RP only; and sex and PTV/Lung predicted grade {>=}2 RP only. Among patients who developed high-grade RP, MLD and PTV/Lung were significantly lower in patients aged {>=}70 years than in younger patients (p<0.05 for both comparisons). Conclusions: The predictors were not completely consistent between grade {>=}2 RP and grade {>=}3 RP. Elderly patients had a higher risk of severe RP than younger patients did, possibly due to lower tolerance of radiation to the lung.

  5. Customized chemotherapy based on epidermal growth factor receptor mutation status for elderly patients with advanced non-small-cell lung cancer: a phase II trial

    International Nuclear Information System (INIS)

    Fujita, Shiro; Mio, Tadashi; Katakami, Nobuyuki; Masago, Katsuhiro; Yoshioka, Hiroshige; Tomii, Keisuke; Kaneda, Toshihiko; Hirabayashi, Masataka; Kunimasa, Kei; Morizane, Toshio

    2012-01-01

    Elderly patients are more vulnerable to toxicity from chemotherapy. Activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are associated with enhanced response to EGFR tyrosine-kinase inhibitors. We studied patients with advanced NSCLC for whom treatment was customized based on EGFR mutation status. We screened 57 chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, aged 70 years or older, and with an Eastern Cooperative Oncology Group performance status 0 or 1, for EGFR exon 19 codon 746–750 deletion and exon 21 L858R mutation. Twenty-two patients with EGFR mutations received gefitinib; 32 patients without mutations received vinorelbine or gemcitabine. The primary endpoint was the response rate. The response rate was 45.5% (95% confidence interval [CI]: 24.4%, 67.8%) in patients with EGFR mutations and 18.8% (95% CI: 7.2%, 36.4%) in patients without EGFR mutations. The median overall survival was 27.9 months (95%CI: 24.4 months, undeterminable months) in patients with EGFR mutations and 14.9 months (95%CI: 11.0 months, 22.4 months) in patients without EGFR mutations. In the gefitinib group, grade 3/4 hepatic dysfunction and dermatitis occurred in 23% and 5% of patients, respectively. In patients treated with vinorelbine or gemcitabine, the most common grade 3 or 4 adverse events were neutropenia (47%; four had febrile neutropenia), anemia (13%), and anorexia (9%). No treatment-related deaths occurred. Treatment customization based on EGFR mutation status deserves consideration, particularly for elderly patients who often cannot receive second-line chemotherapy due to poor organ function or comorbidities. This trial is registered at University hospital Medical Information Network-clinical trial registration (http://www.umin.ac.jp/ctr/index/htm) with the registration identification number C000000436

  6. Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

    Energy Technology Data Exchange (ETDEWEB)

    Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Mehta, Par [Department of Radiation Oncology at Rush Copley Medical Center, Aurora, IL (United States); Khan, Atif [Department of Radiation Oncology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Cancer Institute of New Jersey, New Brunswick, NJ (United States); Marsh, James C.; Zusag, Thomas W. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Warren, William H. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Bonomi, Philip [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Liptay, Michael; Faber, L. Penfield [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States)

    2011-11-15

    Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

  7. Non-small cell lung cancer: current status of chemoradiation for locally advanced disease and an update on susceptibility and prevention

    International Nuclear Information System (INIS)

    Byhardt, Roger W.

    1996-01-01

    Locally advanced, inoperable non-small cell lung cancer (NSCLC) afflicts 40,000 patients yearly. The traditional treatment has been radiation therapy (RT) alone with 5 year survival rates averaging around 5%. Recent reports of randomized clinical trials using combined radiochemotherapy suggest significant improvement in survival compared to RT alone. These trials are difficult to evaluate because of differences in dose, timing and sequencing of both the chemotherapy (CT) and the RT. Dr. Byhardt will give an overview of the significant chemoradiation trials, especially with respect to the factors associated with reduction of local failure and distant metastasis. Dr. Tishler will review the biologic rationale of these regimens and make some prognostications about the potential role of new chemotherapy agents, new developments in RT dose-time-fractionation, and new RT technology in future radiochemotherapy trials. While progress continues to be made using the more traditional cancer treatment modalities, investigations in NSCLC epidemiology and prevention are providing new insights regarding susceptibility, etiology, failure risk stratification, and potential avenues of therapeutic intervention. Dr. Spitz will discuss NSCLC as a paradigm of an environmentally induced disease in which host susceptibility may be determined by genetically determined modulation of environmental exposures. A mutagen sensitivity assay can determine individuals at high risk for developing NSCLC if exposed to carcinogens such as those in cigarette smoke. This susceptibility may have prognostic implications that could influence choice of therapy. Highly susceptible individuals can also be selected for special counseling, smoking cessation, with consideration given to chemoprevention. Dr. Gritz will review major work done in this area

  8. Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status.

    Science.gov (United States)

    Goss, Glenwood; Ferry, David; Wierzbicki, Rafal; Laurie, Scott A; Thompson, Joyce; Biesma, Bonne; Hirsch, Fred R; Varella-Garcia, Marileila; Duffield, Emma; Ataman, Ozlem U; Zarenda, Marc; Armour, Alison A

    2009-05-01

    To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status. NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored. Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred. There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors.

  9. Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

    Science.gov (United States)

    Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

    2016-01-01

    The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Consequences of Anatomic Changes and Respiratory Motion on Radiation Dose Distributions in Conformal Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Britton, Keith R.; Starkschall, George; Liu, Helen; Chang, Joe Y.; Bilton, Stephen; Ezhil, Muthuveni; John-Baptiste, Sandra C.; Kantor, Michael; Cox, James D.; Komaki, Ritsuko; Mohan, Radhe

    2009-01-01

    Purpose: To determine the effect of interfractional changes in anatomy on the target and normal tissue dose distributions during course of radiotherapy in non-small-cell lung cancer patients. Methods and Materials: Weekly respiration-correlated four-dimensional computed tomography scans were acquired for 10 patients. Original beam arrangements from conventional and inverse treatment plans were transferred into each of the weekly four-dimensional computed tomography data sets, and the dose distributions were recalculated. Dosimetric changes to the target volumes and relevant normal structures relative to the baseline treatment plans were analyzed by dose-volume histograms. Results: The overall difference in the mean ± standard deviation of the doses to 95% of the planning target volume and internal target volume between the initial and weekly treatment plans was -11.9% ± 12.1% and -2.5% ± 3.9%, respectively. The mean ± standard deviation change in the internal target volume receiving 95% of the prescribed dose was -2.3% ± 4.1%. The overall differences in the mean ± standard deviation between the initial and weekly treatment plans was 3.1% ± 6.8% for the total lung volume exceeding 20 Gy, 2.2% ± 4.8% for mean total lung dose, and 34.3% ± 43.0% for the spinal cord maximal dose. Conclusion: Serial four-dimensional computed tomography scans provided useful anatomic information and dosimetric changes during radiotherapy. Although the observed dosimetric variations were small, on average, the interfractional changes in tumor volume, mobility, and patient setup was sometimes associated with dramatic dosimetric consequences. Therefore, for locally advanced lung cancer patients, efforts to include image-guided treatment and to perform repeated imaging during the treatment course are recommended

  11. Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study

    International Nuclear Information System (INIS)

    Catalano, G.; Jereczek-Fossa, B.A.; Pas, T. de; Leon, M.E.; Cattani, F.; Spaggiari, L.; Veronesi, G.; Braud, F. de; Orecchia, R.

    2005-01-01

    Purpose: to evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA-IIIB non-small cell lung cancer (NSCLC). Patients and methods: iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions. Results: from February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08). Conclusion: in this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC. (orig.)

  12. High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy

    International Nuclear Information System (INIS)

    Gota, Vikram; Kavathiya, Krunal; Doshi, Kartik; Gurjar, Murari; Damodaran, Solai E; Noronha, Vanita; Joshi, Amit; Prabhash, Kumar

    2014-01-01

    Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC). While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Sixteen of 46 patients (35%) had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively). Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively). Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Higher exposure to pemetrexed is associated with grade ≥3 hyponatremia. The pharmacogenetic basis for higher exposure to pemetrexed in Indian patients needs further investigation

  13. Treatment-Related Death during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Studies.

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    Full Text Available Treatment related death (TRD is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC patients treated with concurrent chemoradiotherapy (CCRT, and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients were eligible. The pooled TRD rate (accounting for heterogeneity was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI of TRDs was 1.08 (0.70-1.66 (P = 0.71. Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09-2.07, P = 0.008. No significant difference was found in TRDs between high (≥ 66 Gy and low (< 66 Gy radiation dose during CCRT (P = 0.605. Neither consolidation (P = 0.476 nor induction chemotherapy (P = 0.175 had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study.

  14. Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

    International Nuclear Information System (INIS)

    Minami, Seigo; Tachibana, Isao; Komuta, Kiyoshi; Kawase, Ichiro; Kijima, Takashi; Takahashi, Ryo; Kida, Hiroshi; Nakatani, Takeshi; Hamaguchi, Masanari; Takeuchi, Yoshiko; Nagatomo, Izumi; Yamamoto, Suguru

    2012-01-01

    Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m 2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16. Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC

  15. Patient Experience of Symptoms and Side Effects when Treated with Osimertinib for Advanced Non-Small-Cell Lung Cancer: A Qualitative Interview Substudy.

    Science.gov (United States)

    Rydén, Anna; Blackhall, Fiona; Kim, Hye Ryun; Pillai, Rathi N; Braam, Lauren; Martin, Mona L; Walding, Andrew

    2017-10-01

    Capturing the patient experience during treatment is important to both regulatory authorities and to patients starting treatment. We identified the symptoms and side effects experienced by patients with advanced non-small-cell lung cancer during osimertinib treatment, to understand treatment expectations, satisfaction, and the level of difficulty coping with the side effects experienced during treatment. Qualitative interviews (approximately 4-6 weeks after treatment initiation and again after approximately 4 months of treatment) were conducted during the phase I/II AURA clinical trial of osimertinib, a tyrosine kinase inhibitor of epidermal growth factor receptor-sensitizing and T790M resistance mutations. During the first interview (23 patients), the most commonly reported symptoms/side effects were coughing, itching, tiredness (each reported by 56.5% of patients), and rash (43.5%). During the second interview (21 patients), compared with the first interview, shortness of breath and diarrhea were reported by more patients (57.1 and 38.1%, respectively; both increased from 34.8%); tiredness remained predominant (42.9%); and itching (38.1%), coughing (38.1%), and rash (14.3%) were reported by fewer patients. At both interviews, the most frequently reported symptoms/side effects were also those most often rated by patients for bothersomeness and severity, and generally received mean scores in the low-to-moderate range. However, several rarely expressed symptoms/side effects (e.g., abdominal pain, frequent day time urination) received high bothersomeness ratings. At the second interview, patients were highly satisfied with osimertinib and had a low level of difficulty in coping with side effects during treatment. These data enhance our understanding of patients' experiences of symptoms/side effects, which could increase the accuracy of the osimertinib benefit-risk assessment, guide management of adverse events, and improve the information given to patients

  16. Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Sequist, Lecia V; Besse, Benjamin; Lynch, Thomas J; Miller, Vincent A; Wong, Kwok K; Gitlitz, Barbara; Eaton, Keith; Zacharchuk, Charles; Freyman, Amy; Powell, Christine; Ananthakrishnan, Revathi; Quinn, Susan; Soria, Jean-Charles

    2010-06-20

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non-small-cell lung cancer (NSCLC) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. We studied neratinib, an irreversible pan-ErbB TKI that may overcome T790M. Patients with advanced NSCLC underwent EGFR sequencing of available tumor tissue at enrollment. Those with > or = 12 weeks of prior TKI therapy were placed in arm A if they were EGFR mutation positive or arm B if they were wild-type. Arm C included TKI-naïve patients with adenocarcinoma and light smoking histories (neratinib, initially at 320 mg but subsequently reduced to 240 mg because of excessive diarrhea. The primary end point was objective response rate (RR). One-hundred sixty-seven patients were treated: 91 in arm A, 48 in arm B, and 28 in arm C. Diarrhea was the most common toxicity; grade 3 incidence was 50% at 320 mg but improved to 25% after dose reduction. The RR was 3% in arm A and zero in arms B and C. No patients with known T790M responded. Notably, three of four patients with an exon 18 G719X EGFR mutation had a partial response and the fourth had stable disease lasting 40 weeks. Neratinib had low activity in patients with prior benefit from TKIs and in TKI-naïve patients, potentially because of insufficient bioavailability from diarrhea-imposed dose limitation. Responses were seen in patients with the rare G719X EGFR mutation, highlighting the importance of obtaining comprehensive genetic information on trials of targeted agents.

  17. Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study.

    Science.gov (United States)

    Niho, Seiji; Ohe, Yuichiro; Ohmatsu, Hironobu; Umemura, Shigeki; Matsumoto, Shingo; Yoh, Kiyotaka; Goto, Koichi

    2017-06-01

    We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC). Patients not showing disease progression after induction platinum-based chemotherapy received S-1 at the dose of 40mg/m 2 twice daily for 14 consecutive days, every three weeks, with or without bevacizumab (Bev) at the dose of 15mg/kg. In cases where the induction chemotherapy regimen contained Bev, Bev was used as continuation maintenance chemotherapy where appropriate. The efficacy/toxicity of switch maintenance chemotherapy with S-1 and S-1+Bev was evaluated separately. The primary end point of this study was the treatment success rate at three months after the start of S-1 treatment. Between July 2010 and January 2014, 79 patients were enrolled, of which 78 were found to be eligible for inclusion in this study. The treatment success rate at three months was 28.2% (90% confidence interval (CI), 7.1-17.1%) in the S-1 group and 64.1% (90% CI, 50.0-76.8%) in the S-1+Bev group. The primary endpoint was met in the S-1+Bev group. The median PFS and OS were 2.6 months and 11.0 months in the S-1 group, and 4.6 months and 19.9 months in the S-1+Bev group, respectively. The most common grade three toxicity was neutropenia (10% incidence in the S-1+Bev group). There were no cases of febrile neutropenia. Switch maintenance chemotherapy with S-1 in combination with continuation maintenance chemotherapy with bevacizumab yielded modest efficacy with mild and acceptable toxicities. Copyright © 2017. Published by Elsevier B.V.

  18. A Randomized, Controlled, Multicenter Clinical Trial Comparing Pemetrexed/Cisplatin and Gemcitabine/Cisplatin as First-line Treatment for Advanced Nonsquamous Non-small Cell Lung Cancer

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    Yan HUANG

    2012-10-01

    Full Text Available Background and objective Platinum-based doublet chemotherapy is still the standard first-line treatment for non-small cell lung cancer (NSCLC. Previous studies have demonstrated that pemetrexed combined with platinum had promising efficacy and safety profile in NSCLC, especially in patients with nonsquamous NSCLC. This trial was conducted to evaluate the efficacy and safety of pemetrexed made in China as first-line treatment. Methods The present study was a randomized, controlled, multicenter clinical trial. Patients were randomly assigned (1:1 to receive cisplatin plus pemetrexed chemotherapy (PC group or gemcitabine plus cisplatin (GC group every 3 weeks. The primary end point was progression free survival (PFS and the secondary end points included 1 year survival rate, objective response rate (ORR, survival without grade 3/4 toxicity (SWT3/4 and safety profile. Results A total of 288 patients from 20 institutions across China were enrolled into the study. Based on the Full Analyses Set (FAS, the PFS was 168 days (5.6 months vs 140 days (4.7 months (P=0.16, one year survival rate was 50.0% vs 54.9% (P=0.47, ORR was 24.4% vs 14.2% (P=0.06 in the PC group and the GC group, respectively; Survival without grade 3/4 toxicity was 11.3 months in GC group vs 8.1 months in PC group (P=0.23. In terms of the safety, side effects were less observed on the PC group (81.95% vs 93.75%, P=0.003. The main side effects included leukopenia, neutropenia, emesis, anemia, thrombopenia. Conclusion The both regimens have similar efficacy as the treatment for advanced nonsquamous NSCLC, but pemetrexed plus cisplatin regimen has better safety profile and seems to have longer PFS, which makes it a new option as the first line setting.

  19. Correlation of pre-and post-induction chemotherapy 18-FDG PET findings with histopathology in patients with locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Chan, Andrea M.; Berlangieri, Sam; Ngai, Michael W.

    2009-01-01

    Full text: Objective: To correlate 18F-FDG PET metabolic response to therapy with histopathology and survival, in patients with locally advanced (stage IIl) non-small cell lung carcinoma (NSCLC) receiving induction chemotherapy. Methods: A retrospective review of all patients with stage III NSCLC planned for induction chemotherapy and surgical resection, in whom pre- and post-chemotherapy FDG-PET at Austin Health between 2004 and 2007 was performed. The staging and positive nodal stations as determined by PET was compared to histopathological findings after resection. The tumour response on serial FDG PET was also compared to overall outcome. Results: 9 patients were included. There was a 100 % correlation between pre- or post- chemotherapy nodal staging and final histopathological nodal stage. Ninety percent of all positive nodal stations (9/10) seen on histopathology were correctly localised by pre- or post-chemotherapy FDG PET. Only one patient with a metastatic lymph node at nodal station 9 R could not be localised by prior PET studies. Of the patients in whom a down-staging in tumour status was observed on the postchemotherapy FDG-PET, 83% (5/6) of patients were still alive (follow-up range of 8 to 40 months) as compared with 33% (1/3 ) (follow-up range of 9-13 months) for non-responders. Conclusion: There is good correlation between pre- and/or post- chemotherapy FDG PET and final histopathology for the nodal staging of stage III NSCLC. There is an overall trend for those patients in whom PET resulted in a down-staging of tumour to have a longer survival.

  20. Superiority of conventional intensity-modulated radiotherapy over helical tomotherapy in locally advanced non-small cell lung cancer. A comparative plan analysis

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    Song, C. [National Cancer Center, Research Institute and Hospital, Goyang (Korea, Republic of). Proton Therapy Center; Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Radiation Oncology; Pyo, H.; Kim, J. [Sungkyunkwan Univ. School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of). Dept. of Radiation Oncology; Lim, Y.K.; Kim, D.W.; Cho, K.H. [National Cancer Center, Research Institute and Hospital, Goyang (Korea, Republic of). Proton Therapy Center; Kim, W.C. [Inha Univ. School of Medicine, Incheon (Korea, Republic of). Dept. of Radiation Oncology; Kim, H.J. [Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Radiation Oncology

    2012-10-15

    Purpose: To compare helical tomotherapy (HT) and conventional intensity-modulated radiotherapy (IMRT) using a variety of dosimetric and radiobiologic indexes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Patients and methods: A total of 20 patients with LA-NSCLC were enrolled. IMRT plans with 4-6 coplanar beams and HT plans were generated for each patient. Dose distributions and dosimetric indexes for the tumors and critical structures were computed for both plans and compared. Results: Both modalities created highly conformal plans. They did not differ in the volumes of lung exposed to > 20 Gy of radiation. The average mean lung dose, volume receiving {>=} 30 Gy, and volume receiving {>=} 10 Gy in HT planning were 18.3 Gy, 18.5%, and 57.1%, respectively, compared to 19.4 Gy, 25.4%, and 48.9%, respectively, with IMRT (p = 0.004, p < 0.001, and p < 0.001). The differences between HT and IMRT in lung volume receiving {>=} 10-20 Gy increased significantly as the planning target volume (PTV) increased. For 6 patients who had PTV greater than 700 cm{sup 3}, IMRT was superior to HT for 5 patients in terms of lung volume receiving {>=} 5-20 Gy. The integral dose to the entire thorax in HT plans was significantly higher than in IMRT plans. Conclusion: HT gave significantly better control of mean lung dose and volume receiving {>=} 30-40 Gy, whereas IMRT provided better control of the lung volume receiving {>=} 5-15 Gy and the integral dose to entire thorax. In most patients with PTV greater than 700 cm{sup 3}, IMRT was superior to HT in terms of lung volume receiving {>=} 5-20 Gy. It is therefore advised that caution should be exercised when planning LA-NSCLC using HT. (orig.)

  1. A single-arm, multicenter, safety-monitoring, phase IV study of icotinib in treating advanced non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Hu, Xingsheng; Han, Baohui; Gu, Aiqin; Zhang, Yiping; Jiao, Shun Chang; Wang, Chang-Li; He, Jintao; Jia, Xueke; Zhang, Li; Peng, Jiewen; Wu, Meina; Ying, Kejing; Wang, Junye; Ma, Kewei; Zhang, Shucai; You, Changxuan; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

    2014-11-01

    The phase 3 ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients, and this led to the approval of icotinib for NSCLC by the China Food and Drug Administration. A phase 4 study was conducted to assess the safety and efficacy of icotinib in a broad range of patients with advanced NSCLC across China. This study retrospectively analyzed data from unresectable, recurrent, and/or advanced NSCLC patients who received oral icotinib 125 mg three times per day. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR) and disease control rate (DCR), which were investigated overall and in subgroups such as patients with an EGFR mutation and elderly patients. Between August, 2011 and August, 2012, a total of 6087 advanced NSCLC patients were registered in this study, of which 5549 were evaluable for safety and tumor response. The median age was 63 years (range 21-95 years), and 1571 (28.3%) patients were over the age of 70. The majority of patients were non-smokers, and had adenocarcinoma and stage IV disease. The overall incidence of adverse drug reactions (ADRs) of any grade was 31.5%. The most common ADRs included rash (17.4%) and diarrhea (8.5%), and three patients experienced interstitial lung disease (ILD). The ORR and DCR were 30.0% and 80.6%, respectively, for the overall population, and 33.4% and 81.2%, 30.3% and 80.3%, and 30.4% and 89.3%, for first-line, second-line, and third-line or multiple line subsets, respectively. In 665 EGFR-mutated patients who were evaluable for tumor response, the ORR and DCR were 49.2% (327/665) and 92.3% (614/665), respectively. The data from over 6000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated a favorable toxicity profile and efficacy in the routine clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands.

    Science.gov (United States)

    Pompen, Marjolein; Gok, Murat; Novák, Annoesjka; van Wuijtswinkel, Rob; Biesma, Bonne; Schramel, Franz; Stigt, Jos; Smit, Hans; Postmus, Pieter

    2009-04-01

    Disease management and costs of treatment of patients with unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are not well known. A retrospective medical chart review was performed by collecting data from the time of diagnosis until the time of death or the end of the evaluation period. In addition to the demographic data, information was collected on the overall management of the patient. Hospital resource utilisation data collected included number of outpatient specialist visits, number and length of hospitalisation, type and number of diagnostic and laboratory procedures, type and number of radiotherapy cycles and detailed information on chemotherapy. To evaluate the economic impact of second-line treatment, a distinction was made between patients who received only best supportive care (BSC, group A) and those who received chemotherapy as a second-line treatment in addition to BSC (group B). The study was performed from the hospital perspective and reports on 2005 costs. Of 102 patients, 74 belonged to group A and 28 to group B. Patient management included a multidisciplinary approach, the extent of which depended on symptoms of the disease and presence of metastases. The average total treatment cost per patient per year of unresectable advanced NSCLC in The Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups, hospitalisation was the major cost driver. In group B second-line chemotherapy was the second largest contributor of the costs. In spite of the difference in numbers of treatment lines provided to patients in groups A and B the total average costs per patient per year were comparable. Overall, the management of unresectable advanced NSCLC appeared to conform with current guidelines in The Netherlands. These patients show high medical resource consumption, with hospitalisation being the main cost driver in both groups. As economic arguments are becoming increasingly important in medical decision making on

  3. {sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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    Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Bodner, William R. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Halmos, Balazs; Cheng, Haiying; Perez-Soler, Roman [Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Keller, Steven M. [Department of Cardiothoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Garg, Madhur [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

    2017-02-01

    Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for

  4. A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus

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    Bang Sun-Hwi

    2012-06-01

    Full Text Available Background and Objectives: Non-small-cell lung cancer (NSCLC represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus (HAP has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. Methods: The study involved six patients treated at the East- West Cancer Center (EWCC from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS and progression-free survival (PFS. Results: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD, and the other three showed progressive disease (PD. The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. Conclusion: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

  5. Pretreatment 18F-FDG PET Textural Features in Locally Advanced Non-Small Cell Lung Cancer: Secondary Analysis of ACRIN 6668/RTOG 0235.

    Science.gov (United States)

    Ohri, Nitin; Duan, Fenghai; Snyder, Bradley S; Wei, Bo; Machtay, Mitchell; Alavi, Abass; Siegel, Barry A; Johnson, Douglas W; Bradley, Jeffrey D; DeNittis, Albert; Werner-Wasik, Maria; El Naqa, Issam

    2016-06-01

    In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on (18)F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information. Patients with locally advanced NSCLC underwent (18)F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient's primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address overfitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan-Meier curves and log-rank testing were used to compare outcomes among patient groups. Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm(3), and the optimal SumMean cutpoint for tumors above 93.3 cm(3) was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  6. Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

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    Xiaohui Zeng

    Full Text Available BACKGROUND: Maintenance gefitinib significantly prolonged progression-free survival (PFS compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC after four chemotherapeutic cycles (21 days per cycle of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. METHODS AND FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP threshold of $16,349 (3 × per-capita gross domestic product of China. The sensitivity analyses all suggested that the model was robust. CONCLUSIONS: Maintenance gefitinib

  7. The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.

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    Fei Zhou

    Full Text Available BACKGROUND AND OBJECTIVE: Overexpression of COX-2 is proved to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Two hundred and twelve patients with inoperable stage IIIB-IV NSCLC received first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP methods. RESULTS: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (-1195G/A polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26-4.84 and the significance still existed after the Bonferroni correction. Statistically significant difference was also found in grade 3 or 4 leukopenia (P value = 0.010; OR = 2.82; 95%CI = 1.28-6.20. No other significant association was observed between genotype and toxicity in the study. The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 0.59; 95%CI = 0.39-0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39-0.94, respectively while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14-2.56 and P value = 0.025; OR = 1.65; 95%CI  = 1.06-2.57, respectively. CONCLUSION: This investigation for the first time

  8. Gefitinib versus vinorelbine in chemotherapy-naive elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized, phase II study.

    Science.gov (United States)

    Crinò, Lucio; Cappuzzo, Federico; Zatloukal, Petr; Reck, Martin; Pesek, Milos; Thompson, Joyce C; Ford, Hugo E R; Hirsch, Fred R; Varella-Garcia, Marileila; Ghiorghiu, Serban; Duffield, Emma L; Armour, Alison A; Speake, Georgina; Cullen, Michael

    2008-09-10

    This phase II, open-label, parallel-group study compared gefitinib with vinorelbine in chemotherapy-naïve elderly patients with advanced non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients (age >or= 70 years) were randomly assigned to gefitinib (250 mg/d orally) or vinorelbine (30 mg/m(2) infusion on days 1 and 8 of a 21-day cycle). The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and tolerability. Exploratory end points included epidermal growth factor receptor (EGFR) gene copy number by fluorescent in situ hybridization (FISH). Patients were randomly assigned to gefitinib (n = 97) or to vinorelbine (n = 99). Hazard ratios (HR; gefitinib v vinorelbine) were 1.19 (95% CI, 0.85 to 1.65) for PFS and 0.98 (95% CI, 0.66 to 1.47) for OS. ORR and disease control rates were 3.1% (95% CI, 0.6 to 8.8) and 43.3% (for gefitinib) and 5.1% (95% CI, 1.7 to 11.4) and 53.5% (for vinorelbine), respectively. Overall QOL improvement and PSI rates were 24.3% and 36.6% (for gefitinib) and 10.9% and 31.0% (for vinorelbine), respectively. In the 54 patients who were EGFR FISH-positive, HRs were 3.13 (95% CI, 1.45 to 6.76) for PFS and 2.88 (95% CI, 1.21 to 6.83) for OS. There were fewer treatment-related grade 3 to 5 adverse events with gefitinib (12.8%) than with vinorelbine (41.7%). There was no statistical difference between gefitinib and vinorelbine in efficacy in chemotherapy-naïve, unselected elderly patients with advanced NSCLC, but there was better tolerability with gefitinib. Individuals who were EGFR FISH-positive benefited more from vinorelbine than from gefitinib; this unexpected finding requires further study.

  9. The cost-effectiveness and cost-utility of high-dose palliative radiotherapy for advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Coy, Peter; Schaafsma, Joseph; Schofield, John A.

    2000-01-01

    Purpose: To compute cost-effectiveness/cost-utility (CE/CU) ratios, from the treatment clinic and societal perspectives, for high-dose palliative radiotherapy treatment (RT) for advanced non-small-cell lung cancer (NSCLC) against best supportive care (BSC) as comparator, and thereby demonstrate a method for computing CE/CU ratios when randomized clinical trial (RCT) data cannot be generated. Methods and Materials: Unit cost estimates based on an earlier reported 1989-90 analysis of treatment costs at the Vancouver Island Cancer Centre, Victoria, British Columbia, Canada, are updated to 1997-1998 and then used to compute the incremental cost of an average dose of high-dose palliative RT. The incremental number of life days and quality-adjusted life days (QALDs) attributable to treatment are from earlier reported regression analyses of the survival and quality-of-life data from patients who enrolled prospectively in a lung cancer management cost-effectiveness study at the clinic over a 2-year period from 1990 to 1992. Results: The baseline CE and CU ratios are $9245 Cdn per life year (LY) and $12,836 per quality-adjusted life year (QALY), respectively, from the clinic perspective; and $12,253/LY and $17,012/QALY, respectively, from the societal perspective. Multivariate sensitivity analysis for the CE ratio produces a range of $5513-28,270/LY from the clinic perspective, and $7307-37,465/LY from the societal perspective. Similar calculations for the CU ratio produce a range of $7205-37,134/QALY from the clinic perspective, and $9550-49,213/QALY from the societal perspective. Conclusion: The cost effectiveness and cost utility of high-dose palliative RT for advanced NSCLC compares favorably with the cost effectiveness of other forms of treatment for NSCLC, of treatments of other forms of cancer, and of many other commonly used medical interventions; and lies within the US $50,000/QALY benchmark often cited for cost-effective care

  10. Early Change in Metabolic Tumor Heterogeneity during Chemoradiotherapy and Its Prognostic Value for Patients with Locally Advanced Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Xinzhe Dong

    Full Text Available To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC.From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT. Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH] and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity. SUVmax and metabolic tumor volume (MTV were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS, and overall survival (OS.Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively. Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1% and specificity (80.0%~83.6% than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively. The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034 and PFS (P = 0.007, P = 0.039. In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021 and OS (HR 0.519, P = 0.015.The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be valuable for predicting treatment response

  11. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment.

    Science.gov (United States)

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. The multimodality treatment was feasible, and triple

  12. Malignant pleural effusion cell blocks are substitutes for tissue in EML4-ALK rearrangement detection in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Zhong, J; Li, X; Bai, H; Zhao, J; Wang, Z; Duan, J; An, T; Wu, M; Wang, Y; Wang, S; Wang, J

    2016-12-01

    To evaluate the feasibility of malignant pleural effusions (MPE) as surrogate samples for the detection of echinoderm microtubule-associated protein-like4 (EML4)-anaplastic lymphoma kinase (ALK) and to investigate the prognostic and predictive value of EML4-ALK in MPE of non-small-cell lung cancer (NSCLC). One hundred and nine NSCLC patients were retrospectively analysed. EML4-ALK was identified using paraffin-embedded tumour cells in MPE samples by immunohistochemistry (IHC, Ventana) and confirmed by fluorescence using in situ hybridisation (FISH) and qRT-PCR. The EGFR mutation was determined by MPE, using denaturing high-performance liquid chromatography (DHPLC). A total of 5 out of 109 (4.58%) patients were identified as EML4-ALK rearrangement in MPE by IHC.; In addition to two metachronous samples, the consistency of MPE and tissue for EML4-ALK detection was 100% (21/21), and the sensitivity and specificity were 100% (2/2) and 100% (19/19), respectively. EML4-ALK rearrangement cases were confirmed by FISH and qRT-PCR; the sensitivity were both 100% (2/2) when compared with tissue, and it was 60% (3/5) and 100% (5/5), respectively, when compared with MPE by IHC. The overall response rate (ORR) was 100% (2/2) for patients with EML4-ALK in MPE. Moreover, the PFS of these patients appeared to be prolonged in chemotherapy (9.27 versus 6.53 and versus 4.67 months, P = 0.122), compared with the EGFR mutation and the EGFR/ALK double negative group, respectively. EML4-ALK rearrangement detection in malignant pleural effusions is a complementary method for EML4-ALK detection. VETANA and qRT-PCR are more appropriate for MPE detection. EML4-ALK rearrangement in pleural effusions has a predictive value for treatment. © 2016 John Wiley & Sons Ltd.

  13. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial.

    Science.gov (United States)

    Ridolfi, Laura; Bertetto, Oscar; Santo, Antonio; Naglieri, Emanuele; Lopez, Massimo; Recchia, Francesco; Lissoni, Paolo; Galliano, Marco; Testore, Franco; Porta, Camillo; Maglie, Monica; Dall'agata, Monia; Fumagalli, Luca; Ridolfi, Ruggero

    2011-10-01

    Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100 mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed.

  14. EGFR Mutation Testing in Patients with Advanced Non-Small Cell Lung Cancer: A Comprehensive Evaluation of Real-World Practice in an East Asian Tertiary Hospital

    Science.gov (United States)

    Cho, Juhee; Rampal, Sanjay; Han, Joungho; Parasuraman, Bhash; Guallar, Eliseo; Lee, Genehee; Lee, Jeeyun; Shim, Young Mog

    2013-01-01

    Introduction Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. Methods Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. Results This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. Conclusions In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants

  15. EGFR mutation testing in patients with advanced non-small cell lung cancer: a comprehensive evaluation of real-world practice in an East Asian tertiary hospital.

    Directory of Open Access Journals (Sweden)

    Yoon-La Choi

    Full Text Available INTRODUCTION: Guidelines for management of non-small cell lung cancer (NSCLC strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. METHODS: Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. RESULTS: This cohort had a mean age (SD of 59.6 (11.1 years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5% and squamous cell carcinoma (18.0%. Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001. The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%, pulmonologists (31.9%, and thoracic surgeons (6.6%. EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7% were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. CONCLUSIONS: In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive

  16. The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival

    International Nuclear Information System (INIS)

    Bergqvist, Michael; Brattström, Daniel; Larsson, Anders; Hesselius, Patrik; Brodin, Ola; Wagenius, Gunnar

    2004-01-01

    Lung cancer causes approximately one million deaths each year worldwide and protein p53 has been shown to be involved in the intricate processes regulating response to radiation and/or chemotherapeutic treatment. Consequently, since antibodies against p53 (anti-p53 antibodies) are associated with mutations within the p53 gene it seems likely that these antibodies could, hypothetically, be correlated with prognosis. Serum samples from patients with non-small cell lung cancer (NSCLC) admitted to the Department of Oncology, University Hospital, Uppsala, Sweden, during 1983–1996 were studied. Anti-p53 abs were measured using a sandwich ELISA (Dianova, Hamburg, Germany). The present study included 84 patients with stage IIIA-IV (advanced NSCLC). At least three serum samples from each patient were collected and altogether 529 serum samples were analysed for the presence of anti-p53 antibodies. The median value of anti-p53 antibodies was 0.06 (range 0 – 139.8). Seventeen percent of investigated NSCLC first serum samples (n = 84) expressed elevated levels of anti-p53 antibodies. Anti-p53 antibodies were not correlated to tumour volume or platelets. Survival analysis showed that anti-p53 antibodies were not associated with survival as revealed by univariate analysis (p = 0.29). However, patients with adenocarcinoma had a significantly poorer survival if they expressed anti-p53 antibodies (p = 0.01), whereas this was not found for patients with squamous cell carcinoma (p = 0.13). In patients where the blood samples were collected during radiation therapy, a statistically significant correlation towards poorer survival was found (p = 0.05) when elevated anti-p53 antibodies levels were present. No correlations to survival were found for serum samples collected prior to radiation therapy, during chemotherapy, or during follow-up. When anti-p53 antibodies were measured continuously, no increase in median anti-p53 values was observed the closer the individual patient come to

  17. Insulin-like Growth Factor Receptor 1 mRNA Expression as a Prognostic Marker in Advanced Non-small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Vilmar, Adam; Santoni-Rugiu, Eric; Cillas, Jesus Garcia-Fon

    2014-01-01

    BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) has yet to be established as a biomarker in non-small cell lung cancer (NSCLC) but could prove useful in customized chemotherapy. We explored its prognostic value using both quantitative real-time reverse transcriptase polymerase chain......-points. RESULTS: Surgical tissue samples were available from 33 patients deemed inoperable. IGF1R status varied according to histopathology. Patients with tumors positive for IGF1R mRNA expression had a shorter progression-free and overall survival when compared to the negative sub-group (6.1 vs. 7.4 months, p=0...

  18. A competing risk model of first failure site after definitive (chemo) radiation therapy for locally advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Nygård, Lotte; Vogelius, Ivan R; Fischer, Barbara M

    2018-01-01

    INTRODUCTION: The aim of the study was to build a model of first failure site and lesion specific failure probability after definitive chemo-radiotherapy for inoperable non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 251 patients receiving definitive chemo......-regional failure, multivariable logistic regression was applied to assess risk of each lesion being first site of failure. The two models were used in combination to predict lesion failure probability accounting for competing events. RESULTS: Adenocarcinoma had a lower hazard ratio (HR) of loco-regional (LR...

  19. Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Leonard, Kara Lynne [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Safran, Howard [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Ng, Thomas [Division of Thoracic Surgery, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Taber, Angela [Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Khurshid, Humera; Birnbaum, Ariel [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Wazer, David E.; DiPetrillo, Thomas [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States)

    2016-12-01

    Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24

  20. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report

    Directory of Open Access Journals (Sweden)

    María Espinosa Bosch

    2016-07-01

    Full Text Available Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5–12.6] vs. 7.9 months [6.7–9.1]; HR 0.75 [95% CI 0.60–0.92], p=0.0073. The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER per year of life with PFS in the overall population of 134,274.47 € (notified price. In the adenocarcinoma population per each life of year gained (LYG, the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and

  1. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

    Directory of Open Access Journals (Sweden)

    Wenhua Liang

    Full Text Available Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons.We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR, progression free survival (PFS, overall survival (OS were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs based on Bayesian network integrated the efficacy and specific toxicities of all included treatments.Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, P<0.00001; 1-year PFS: 42.9% vs. 9.7%, OR 7.83, 95%CI 4.50 to 13.61; P<0.00001 through direct meta-analysis. In the network meta-analyses, no statistically significant differences in efficacy were found between these four TKIs with respect to all outcome measures. Trend analyses of rank probabilities revealed that the cumulative probabilities of being the most efficacious treatments were (ORR, 1-year PFS, 1-year OS, 2-year OS: erlotinib (51%, 38%, 14%, 19%, gefitinib (1%, 6%, 5%, 16%, afatinib (29%, 27%, 30%, 27% and icotinib (19%, 29%, NA, NA, respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib.The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed

  2. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    International Nuclear Information System (INIS)

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-01-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit

  3. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    International Nuclear Information System (INIS)

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-01-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  4. SU-E-J-244: Development and Validation of a Knowledge Based Planning Model for External Beam Radiation Therapy of Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Z; Kennedy, A [Sarah Cannon, Nashville, TN (United States); Larsen, E; Hayes, C; Grow, A [North Florida Cancer Center, Gainesville, FL (United States); Bahamondes, S.; Zheng, Y; Wu, X [JFK Comprehensive Cancer Institute, Lake Worth, FL (United States); Choi, M; Pai, S [Good Samaritan Hospital, Los Gatos, CA (United States); Li, J [Doctors Hospital of Augusta, Augusta, GA (United States); Cranford, K [Trident Medical Center, Charleston, SC (United States)

    2015-06-15

    Purpose: The study aims to develop and validate a knowledge based planning (KBP) model for external beam radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). Methods: RapidPlan™ technology was used to develop a lung KBP model. Plans from 65 patients with LA-NSCLC were used to train the model. 25 patients were treated with VMAT, and the other patients were treated with IMRT. Organs-at-risk (OARs) included right lung, left lung, heart, esophagus, and spinal cord. DVH and geometric distribution DVH were extracted from the treated plans. The model was trained using principal component analysis and step-wise multiple regression. Box plot and regression plot tools were used to identify geometric outliers and dosimetry outliers and help fine-tune the model. The validation was performed by (a) comparing predicted DVH boundaries to actual DVHs of 63 patients and (b) using an independent set of treatment planning data. Results: 63 out of 65 plans were included in the final KBP model with PTV volume ranging from 102.5cc to 1450.2cc. Total treatment dose prescription varied from 50Gy to 70Gy based on institutional guidelines. One patient was excluded due to geometric outlier where 2.18cc of spinal cord was included in PTV. The other patient was excluded due to dosimetric outlier where the dose sparing to spinal cord was heavily enforced in the clinical plan. Target volume, OAR volume, OAR overlap volume percentage to target, and OAR out-of-field volume were included in the trained model. Lungs and heart had two principal component scores of GEDVH, whereas spinal cord and esophagus had three in the final model. Predicted DVH band (mean ±1 standard deviation) represented 66.2±3.6% of all DVHs. Conclusion: A KBP model was developed and validated for radiotherapy of LA-NSCLC in a commercial treatment planning system. The clinical implementation may improve the consistency of IMRT/VMAT planning.

  5. Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warner, Andrew [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada); Dahele, Max [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Hu, Bo; Palma, David A. [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Oberije, Cary [Department of Radiation Oncology, MAASTRO Clinic, Maastricht (Netherlands); Tsujino, Kayoko [Department of Radiation Oncology, Hyogo Cancer Center, Akashi (Japan); Moreno-Jimenez, Marta [Department of Oncology, Clínica Universidad, Universidad de Navarra, Pamplona (Spain); Kim, Tae Hyun [Department of Radiation Oncology, National Cancer Center, Goyang-si, Gyeonggi (Korea, Republic of); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina (United States); Rengan, Ramesh [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); De Petris, Luigi [Department of Oncology and Pathology, Karolinska University Hospital, Stockholm (Sweden); Ramella, Sara [Department of Radiation Oncology, Campus Bio-Medico University, Rome (Italy); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); De Dios, Núria Rodriguez [Department of Radiation Oncology, Hospital de la Esperanza, Parc de Salut Mar, Barcelona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Rodrigues, George, E-mail: George.Rodrigues@lhsc.on.ca [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada)

    2016-03-01

    Purpose: Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis. Methods and Materials: Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-day survival based on important predictors from RPA. Results: Median follow-up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] ≥100 cm{sup 3}: 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV{sub 1}], defined as the ratio of FEV{sub 1} to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm{sup 3} or GTV ≥100 cm{sup 3} and FEV{sub 1} ≥80%) and high-risk (GTV ≥100 cm{sup 3} and FEV{sub 1} <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV{sub 1}, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R{sup 2} = 0

  6. nab-Paclitaxel/carboplatin in elderly patients with advanced squamous non-small cell lung cancer: a retrospective analysis of a Phase III trial

    Directory of Open Access Journals (Sweden)

    Gridelli C

    2018-05-01

    Full Text Available Cesare Gridelli,1 Tianlei Chen,2 Amy Ko,2 Mary E O’Brien,3 Teng Jin Ong,4 Mark A Socinski,5 Pieter E Postmus6 1Division of Medical Oncology, S. G. Moscati Hospital, Avellino, Italy; 2Biostatistics, Celgene Corporation, Summit, NJ, USA; 3Medical Oncology, Royal Marsden Hospital, London, UK; 4Medical Affairs, Celgene Corporation, Summit, NJ, USA; 5Lung Cancer & Esophageal Cancer, Florida Hospital Cancer Institute, Orlando, FL, USA; 6Pulmonary Diseases, Clatterbridge Cancer Center, Liverpool, UK Background: Limited data on elderly patients with squamous advanced non-small cell lung cancer (NSCLC preclude optimal treatment. Here, we report the outcomes of a retrospective analysis of a subset of patients ≥70 years with squamous histology from the Phase III trial that evaluated nab-paclitaxel/carboplatin vs paclitaxel/carboplatin. Patients and methods: Patients with stage IIIB/IV NSCLC received (1:1 nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 or paclitaxel 200 mg/m2 on day 1, both with carboplatin area under the curve 6 mg×min/mL on day 1 every 3 weeks. The primary endpoint was independently assessed overall response rate as per the Response Evaluation Criteria in Solid Tumors v1.0. Secondary endpoints included progression-free survival, overall survival, and safety. Results: Sixty-five patients ≥70 years with squamous histology were included (nab-paclitaxel/carboplatin, n=35; paclitaxel/carboplatin, n=30. nab-Paclitaxel/carboplatin vs paclitaxel/carboplatin, respectively, resulted in an overall response rate of 46% vs 20% (response rate ratio, 2.29, P=0.029 and a median overall survival of 16.9 vs 8.6 months (hazard ratio, 0.50, P=0.018. No difference was observed in median progression-free survival (5.7 months for both. Incidences of grade 3/4 neutropenia (50% vs 63%, leukopenia (29% vs 37%, fatigue (3% vs 13%, and peripheral neuropathy (3% vs 13% were lower, but those of thrombocytopenia (21% vs 10% and anemia (21% vs 7% were higher with

  7. Results of paclitaxel (day 1 and 8 and carboplatin given on every three weeks in advanced (stage III-IV non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Salepci Taflan

    2005-01-01

    Full Text Available Abstract Background Both paclitaxel (P and carboplatin (C have significant activity in non-small cell lung cancer (NSCLC. The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT regimen in advanced stage NSCLC to evaluate the efficacy and toxicity. Methods Patients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS ECOG 0–2 were given P 112.5 mg/m2 intravenously (IV over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles. Results Median age was 58 (age range 39–77 and 41 patients (80% were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1–6. Seven patients (14% did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR in 45% and stable disease (SD in 18%. Twelve patients (24% received local RT. Thirteen patients (25% received 2nd line CT at progression. At a median follow-up of 7 months (range, 1–20, 25 (49% patients died and 35 patients (69% progressed. Median overall survival (OS was 11 ± 2 months (95% CI; 6 to 16, 1-year OS ratio was 44%. Median time to progression (TTP was 6 ± 1 months (95% CI; 4 to 8, 1-year progression free survival (PFS ratio was 20%. We observed following grade 3 toxicities: asthenia (10%, neuropathy (4%, anorexia (4%, anemia (4%, hypersensitivity to P (2%, nausea/vomiting (2%, diarrhea (2% and neutropenia (2%. Two patients (4% died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%. Conclusions P on day 1 and 8 and C every three weeks is practical and fairly

  8. Prognostic model for long-term survival of locally advanced non-small-cell lung cancer patients after neoadjuvant radiochemotherapy and resection integrating clinical and histopathologic factors

    International Nuclear Information System (INIS)

    Pöttgen, Christoph; Stuschke, Martin; Graupner, Britta; Theegarten, Dirk; Gauler, Thomas; Jendrossek, Verena; Freitag, Lutz; Jawad, Jehad Abu; Gkika, Eleni; Wohlschlaeger, Jeremias; Welter, Stefan; Hoiczyk, Matthias; Schuler, Martin; Stamatis, Georgios; Eberhardt, Wilfried

    2015-01-01

    Outcome of consecutive patients with locally advanced non-small cell lung cancer and histopathologically proven mediastional lymph node metastases treated with induction chemotherapy, neoadjuvant radiochemotherapy and thoracotomy at the West German Cancer Center between 08/2000 and 06/2012 was analysed. A clinico-pathological prognostic model for survival was built including partial or complete response according to computed tomography imaging (CT) as clinical parameters as well as pathologic complete remission (pCR) and mediastinal nodal clearance (MNC) as histopathologic factors. Proportional hazard analysis (PHA) and recursive partitioning analysis (RPA) were used to identify prognostic factors for survival. Long-term survival was defined as survival ≥ 36 months. A total of 157 patients were treated, median follow-up was 97 months. Among these patients, pCR and MNC were observed in 41 and 85 patients, respectively. Overall survival was 56 ± 4% and 36 ± 4% at 24 and 60 months, respectively. Sensitivities of pCR and MNC to detect long-term survivors were 38% and 61%, specificities were 84% and 52%, respectively. Multivariable survival analysis revealed pCR, cN3 category, and gender, as prognostic factors at a level of α < 0.05. Considering only preoperative available parameters, CT response became significant. Classifying patients with a predicted hazard above the median as high risk group and the remaining as low risk patients yielded better separation of the survival curves by the inclusion of histopathologic factors than by preoperative factors alone (p < 0.0001, log rank test). Using RPA, pCR was identified as the top prognostic factor above clinical factors (p = 0.0006). No long term survivors were observed in patients with cT3-4 cN3 tumors without pCR. pCR is the dominant histopathologic response parameter and improves prognostic classifiers, based on clinical parameters. The validated prognostic model can be used to estimate individual prognosis and

  9. Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

    Directory of Open Access Journals (Sweden)

    Jonathan González García

    2017-01-01

    Full Text Available Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC, and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years. The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem, cisplatin/gemcitabine/ bevacizumab (cis/gem/bev, and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev. The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V., due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

  10. Adaptive/Nonadaptive Proton Radiation Planning and Outcomes in a Phase II Trial for Locally Advanced Non-small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koay, Eugene J.; Lege, David [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Cox, James D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-12-01

    Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall

  11. Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Sim, Sang; Rosenzweig, Kenneth E.; Schindelheim, Rachel; Ng, Kenneth K.; Leibel, Steven A.

    2001-01-01

    Purpose: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. Results: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p=0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p=0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. Conclusion: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher

  12. Meta-analysis of published efficacy and safety data for docetaxel in second-line treatment of patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Stroh, Mark; Green, Michelle; Cha, Edward; Zhang, Nancy; Wada, Russ; Jin, Jin

    2016-03-01

    To gain a better understanding of the impact of dose and other prognostic factors on safety and efficacy of docetaxel in second-line non-small-cell lung cancer patients. A model-based meta-analysis (MBMA) of a published docetaxel monotherapy data in 6085 second-line non-small-cell lung cancer patients from 46 trials was conducted. The logit of grade 3/4 neutropenia incidence was a linear function of dose, with a 5% increase in the odds of neutropenia per mg/m(2) increase in dose [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.04-1.06], and a Japanese study effect (OR 17.1, 95% CI 6.05-48.4). The logit of overall response rate (ORR) was a linear function of cumulative dose (0.4% increase in the odds of response per mg/m(2) increase; OR 1.004, 95% CI 1.001-1.008) and median population age (OR 1.08 per year, 95% CI 1.02-1.15). A Japanese study effect was identified for overall survival (OS) in addition to prognostic factors identified by a previous meta-analysis. This current MBMA identified docetaxel dose-response relationships for both neutropenia and ORR, an effect of age on ORR, and Japanese study effects on both neutropenia and OS.

  13. Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer

    OpenAIRE

    Veldore,Vidya; Choughule,Anuradha; Routhu,Tejaswi; Mandloi,Nitin; Noronha,Vanita; Joshi,Amit; Dutt,Amit; Gupta,Ravi; Vedam,Ramprasad; Prabhash,Kumar

    2018-01-01

    Vidya H Veldore,1,* Anuradha Choughule,2,* Tejaswi Routhu,1 Nitin Mandloi,1 Vanita Noronha,2 Amit Joshi,2 Amit Dutt,3 Ravi Gupta,1 Ramprasad Vedam,1 Kumar Prabhash2 1MedGenome Labs Private Ltd,, Bangalore, India; 2Tata Memorial Centre, Parel, Mumbai, India; 3The Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai, Maharashtra, India *These authors contributed equally to this work Abstract: Plasma cell-free tumor DNA, or circulating tumo...

  14. Clinical efficacy of first-generation EGFR-TKIs in patients with advanced non-small-cell lung cancer harboring EGFR exon 20 mutations

    Directory of Open Access Journals (Sweden)

    Chen D

    2016-07-01

    Full Text Available Dan Chen,1 Zhengbo Song,2 Guoping Cheng3 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Chemotherapy, 3Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Purpose: Subsets of non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR mutations carry uncommon subtypes. We evaluated the efficacy of first-generation EGFR-tyrosine kinase inhibitors (TKIs; erlotinib, gefitinib, and icotinib in patients with non-small-cell lung cancer carrying insertions and T790M and S768I mutations in EGFR exon 20. Patients and methods: Patients carrying EGFR exon 20 insertion/T790M/S768I mutations and treated with EGFR-TKIs were evaluated from 2005 to 2014 in Zhejiang Cancer Hospital. The efficacy was evaluated using the Kaplan–Meier method and compared with the log-rank test. Results: Sixty-two patients with exon 20 insertion/T790M/S768I mutations were enrolled. Mutations including exon 20 insertions and T790M and S768I mutations were observed in 29, 23, and ten patients, respectively. In total, the response rate and median progression-free survival (PFS were 8.1% and 2.1 months, respectively. Patients with S768I mutation manifested the longest median PFS (2.7 months, followed by those with T790M (2.4 months and exon 20 insertions (1.9 months; P=0.022. Patients with complex mutations show a better PFS than those with single mutations (2.7 months vs 1.9 months; P=0.034. Conclusion: First-generation EGFR-TKIs are less effective in patients with exon 20 uncommon mutations than in those with common mutations. Patients with complex mutations benefited more from first-generation EGFR-TKIs than those with single mutations. Keywords: non-small cell lung cancer, epidermal growth factor receptor, EGFR mutations, exon 20, tyrosine kinase inhibitor

  15. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

    Directory of Open Access Journals (Sweden)

    Babu KG

    2014-06-01

    Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

  16. Oligometastatic non-small-cell lung cancer: current treatment strategies

    Directory of Open Access Journals (Sweden)

    Richard PJ

    2016-11-01

    Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

  17. A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

    Directory of Open Access Journals (Sweden)

    Taipale K

    2017-08-01

    Full Text Available Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS and overall survival (OS relative to gemcitabine + cisplatin (induction sequences or best supportive care (BSC (maintenance sequences. Modeled health-care benefits were expressed as life-years (LYs and quality-adjusted LYs (QALYs (estimated using French EuroQol five-dimension questionnaire tariffs. The study was conducted from the payer perspective (National Health Insurance. Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed

  18. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    Directory of Open Access Journals (Sweden)

    Bonanno L

    2016-06-01

    Full Text Available Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs. No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1, paclitaxel (200 mg/m2, d1, and gemcitabine (1,000 mg/m2 d1, 8 for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS and overall survival (OS were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system. A total of 36 (62% patients achieved partial response (PR, and six (10% progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62% cases. After chemotherapy, 37 (64% patients underwent surgery

  19. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin and celeco......Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin...... and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFN EliSpot. Secondary objec- tives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten...

  20. Cost-Effectiveness Analysis of Afatinib versus Gefitinib for First-Line Treatment of Advanced EGFR-Mutated Advanced Non-Small Cell Lung Cancers.

    Science.gov (United States)

    Chouaid, Christos; Luciani, Laura; LeLay, Katell; Do, Pascal; Bennouna, Jaafar; Perol, Maurice; Moro-Sibilot, Denis; Vergnenègre, Alain; de Pouvourville, Gérard

    2017-10-01

    The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. For all EGFR mutation-positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation-positive NSCLCs. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  1. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.

    Science.gov (United States)

    Heymach, John V; Paz-Ares, Luis; De Braud, Filippo; Sebastian, Martin; Stewart, David J; Eberhardt, Wilfried E E; Ranade, Anantbhushan A; Cohen, Graham; Trigo, Jose Manuel; Sandler, Alan B; Bonomi, Philip D; Herbst, Roy S; Krebs, Annetta D; Vasselli, James; Johnson, Bruce E

    2008-11-20

    Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.

  2. (99m)Tc-3PRGD 2 SPECT/CT predicts the outcome of advanced nonsquamous non-small cell lung cancer receiving chemoradiotherapy plus bevacizumab.

    Science.gov (United States)

    Ma, Qingjie; Min, Kaiyin; Wang, Ting; Chen, Bin; Wen, Qiang; Wang, Fan; Ji, Tiefeng; Gao, Shi

    2015-07-01

    Functional imaging can help clinicians assess the individual response of advanced nonsquamous non-small cell lung cancer (NSCLC) to chemoradiation therapy plus bevacizumab. Our purpose is to investigate the ability of (99m)Tc-3PRGD2 single photon emission computed tomography/computed tomography (SPECT/CT) in predicting the early response to treatment. Patients with advanced nonsquamous NSCLC diagnosed by histological or cytological examination were imaged with (99m)Tc-3PRGD2 SPECT/CT at 3 time points: 1-3 days before the start of treatment (SPECT1), 40 Gy radiotherapy with 2 cycles of chemotherapy plus bevacizumab (SPECT2) and 4 weeks after chemoradiotherapy plus bevacizumab (SPECT3). The images were evaluated semiquantitatively by measuring the tumor to non-tumor ratio (T/N) and calculating the percentage change in T/N ratio. Short-term outcome was assessed by the treatment response evaluation according to the Response Evaluation Criteria in Solid Tumors criteria as: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients were divided two groups: responders (CR and PR) and nonresponders (SD and PD). To determine a threshold for percent reduction in T/N ratios, receiver-operating characteristic (ROC) curve analysis was used. Patients were grouped again based on the threshold of P1 (the change percentage from SPECT1 to SPECT2) and P2 (the change percentage from SPECT1 to SPECT3): P1 responders and P1 nonresponders; P2 responders and P2 nonresponders. Patients were followed up starting 4 weeks after completion of therapy and then every 3 months for the first 2 years and every 6 months after 2 years. OS of P1 responders, P1 nonresponders, P2 responders and P2 nonresponders was estimated and graphically illustrated using the Kaplan-Meier method and the log-rank test was used to test the null hypotheses of equal OS in subgroups of patients. A total of 28 patients completed all imaging and treatment. All primary

  3. Patterns of metastatic progression after definitive radiation therapy for early-stage and locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Jensen, Garrett L; Tang, Chad; Hess, Kenneth R; Liao, Zhongxing; Gomez, Daniel R

    2017-06-01

    Current preclinical models of metastatic disease (particularly oligometastases) suggest that metastases appear in a hierarchical order. We attempted to identify systematic patterns of metastasis in non-small cell lung cancer (NSCLC) after radiation therapy (XRT). We analyzed 1074 patients treated from 12/21/1998 through 8/20/2012 with ≥60 Gy definitive radiation for initially non-metastatic NSCLC. Location and time of metastases were recorded. Regional nodal failure was noted, as was subsequent distal failure. For further analysis, we considered only the five most common sites of metastasis (bone, brain, liver, adrenal, and lung). Metastatic progression over time was defined and patterns elucidated with Chi square tests. Histologic findings were analyzed with Wilcoxon rank sum tests. A significant multistep linear progression was not apparent. Having a first metastasis in lung or bone was associated with respective 16% (median 2.4 months) and 15% likelihoods (median 7.9 months) of secondary brain metastasis. Initial metastasis in the brain led to metastasis in another organ 29.3% of the time, most often in the lung, bone, and liver (medians 3.6, 7.9, and 3.1 months). Adenocarcinoma was more likely than squamous to metastasize to the brain (18 vs. 9%) and any of the five major sites (41 vs. 27%). We did not appreciate dominant patterns suggesting a multi-step hierarchical order of metastasis. Rather, our findings suggest that certain subgroups may develop different patterns of spread depending on a variety of factors.

  4. Radiomic biomarkers from PET/CT multi-modality fusion images for the prediction of immunotherapy response in advanced non-small cell lung cancer patients

    Science.gov (United States)

    Mu, Wei; Qi, Jin; Lu, Hong; Schabath, Matthew; Balagurunathan, Yoganand; Tunali, Ilke; Gillies, Robert James

    2018-02-01

    Purpose: Investigate the ability of using complementary information provided by the fusion of PET/CT images to predict immunotherapy response in non-small cell lung cancer (NSCLC) patients. Materials and methods: We collected 64 patients diagnosed with primary NSCLC treated with anti PD-1 checkpoint blockade. Using PET/CT images, fused images were created following multiple methodologies, resulting in up to 7 different images for the tumor region. Quantitative image features were extracted from the primary image (PET/CT) and the fused images, which included 195 from primary images and 1235 features from the fusion images. Three clinical characteristics were also analyzed. We then used support vector machine (SVM) classification models to identify discriminant features that predict immunotherapy response at baseline. Results: A SVM built with 87 fusion features and 13 primary PET/CT features on validation dataset had an accuracy and area under the ROC curve (AUROC) of 87.5% and 0.82, respectively, compared to a model built with 113 original PET/CT features on validation dataset 78.12% and 0.68. Conclusion: The fusion features shows better ability to predict immunotherapy response prediction compared to individual image features.

  5. Brief report: Afatinib and cetuximab in four patients with EGFR exon 20 insertion positive advanced non-small-cell lung cancer.

    Science.gov (United States)

    van Veggel, Bianca; de Langen, Adrianus J; Hashemi, Sayed; Monkhorst, Kim; Heideman, Daniëlle A M; Thunnissen, Erik; Smit, Egbert F

    2018-04-24

    Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-9% of EGFR mutated non-small-cell lung cancer (NSCLC). Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses. Four patients with EGFR exon 20 insertion positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250-500 mg/m 2 every two weeks. All patients had stage IV adenocarcinoma of the lung harboring an EGFR exon 20 insertion mutation. Previous lines of treatment consisted of platinum doublet chemotherapy (n=4) and EGFR TKI (n=2). Three out of four patients showed a partial response according to RECIST 1.1. Median progression-free survival was 5.4 months (95% confidence interval 0.0 - 14.2 months; range 2.7 - 17.6 months). Toxicity was manageable with appropriate skin management and dose reduction being required in two patients. Dual EGFR blockade with afatinib and cetuximab may induce tumor responses in patients with EGFR exon 20 insertion positive NSCLC. Copyright © 2018. Published by Elsevier Inc.

  6. High prevalence of malnutrition and deranged relationship between energy demands and food intake in advanced non-small cell lung cancer.

    Science.gov (United States)

    Mohan, A; Poulose, R; Kulshreshtha, I; Chautani, A M; Madan, K; Hadda, V; Guleria, R

    2017-07-01

    The relation between dietary intake and metabolic profile in non-small cell lung cancer (NSCLC) was evaluated. Patients with NSCLC were recruited and their caloric requirement and resting energy expenditure (REE) were calculated using the Harris-Benedict equation and Katch-McArdle formula respectively. Hypermetabolic state was defined as REE more than 10% above the basal metabolic rate (BMR). Body composition parameters were calculated by bioelectric impedance method. The 24-h dietary intake method and Malnutrition Universal Screening Tool assessed nutritional intake. One hundred and forty-eight subjects were included (87% males). Of these, 46.6% subjects were hypermetabolic and 31% cachexic, with lower calorie and protein intakes than recommended, although per cent of total energy derived from protein, fat and carbohydrates were similar. Hypermetabolic patients had lower BMI, though the per cent deficit in energy and protein consumption was similar. Cachexia was associated with lower BMR but not with deficit in energy or protein consumption. No correlation was seen between dietary intake and body composition parameters. The calorie and protein intake of NSCLC patients is lower than recommended. The discordance between elevated REE and dietary intake implies that the relationship between increased energy demands and food intake may be altered. © 2016 John Wiley & Sons Ltd.

  7. Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

    International Nuclear Information System (INIS)

    Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

    2011-01-01

    Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

  8. Comparison of two dimensional and three dimensional radiotherapy treatment planning in locally advanced non-small cell lung cancer treated with continuous hyperfractionated accelerated radiotherapy weekend less

    International Nuclear Information System (INIS)

    Wilson, Elena M.; Joy Williams, Frances; Ethan Lyn, Basil; Aird, Edwin G.A.

    2005-01-01

    Background and purpose: Patients with inoperable non-small cell lung cancer being treated with continuous hyperfractionated accelerated radiotherapy weekend less (CHARTWEL) were planned and treated with a three dimensional (3D) conformal protocol and comparison made with two dimensional (2D) planning, as used previously, to compare past practice and methods. Patients and methods: Twenty-four patients were planned initially using 3D and then replanned using a 2D system. The 2D plans were transferred onto the 3D system and recalculated. Dose volume histograms could then be constructed of planning target volumes for phases 1 and 2 (PTV 1 and 2, respectively), lung and spinal cord for the 2D plans and compared with the 3D plans. Results: There was a significantly lower absolute dose to the isocentre with 2D compared to 3D planning with dose reductions of 3.9% for phase 1, 4.4% for phase 2 and 4.7% for those treated with a single phase. Maximum dose to spinal cord was greater in 17 of the 24 2D plans with a median dose reduction of 0.82 Gy for 3D (P=0.04). The percentage volume of whole lung receiving ≥20 Gy (V 20 ) was greater in 16 of the 24 2D plans with a median reduction in V 20 of 2.4% for 3D (P=0.03). Conclusions: A lower dose to tumour was obtained using 2D planning due to the method of dose calculation and spinal cord and lung doses were significantly higher

  9. Role of [18F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Caicedo, Carlos; Garcia-Velloso, Maria Jose; Vigil Diaz, Carmen; Richter Echevarria, Jose Angel; Lozano, Maria Dolores; Labiano, Tania; Lopez-Picazo, Jose Maria; Gurpide, Alfonso; Perez Gracia, Jose Luis; Zulueta, Javier

    2014-01-01

    The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [ 18 F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC. Between January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [ 18 F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [ 18 F]FDG PET/CT for predicting KRAS mutation. From 102 patients staged using [ 18 F]FDG PET/CT, 28 (27 %) had KRAS mutation (KRAS+), 22 (22 %) had EGFR mutation (EGFR+) and 52 (51 %) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [ 18 F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p 18 F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (p 18 F]FDG uptake than WT patients, as assessed in terms of SUVpeak, SUVmax and SUVmean. A multivariate model based on age, gender, AJCC stage and SUVmean might be used as a predictive marker of KRAS mutation status in patients with stage III or IV NSCLC. (orig.)

  10. Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer.

    Science.gov (United States)

    Leighl, Natasha B; Shepherd, Frances A; Kwong, Rita; Burkes, Ronald L; Feld, Ronald; Goodwin, Pamela J

    2002-03-01

    To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non-small-cell lung cancer. A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada's public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data. The incremental survival benefit in the docetaxel arm over BSC was 2 months (P =.047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m(2), the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of drugs, investigations, radiotherapy, and community care. BSC patients had fewer hospitalizations than patients in the chemotherapy arm and were more often palliated at home. Although the decision to treat should not be based on economic considerations alone, our CE estimate of $31,776 per year of life gained (at the currently recommended dose of docetaxel) is within an acceptable range of health care expenditures, and the total costs of therapy are similar to those of second-line palliative chemotherapy for other solid tumors.

  11. Circulating Endothelial-Derived Activated Microparticle: A Useful Biomarker for Predicting One-Year Mortality in Patients with Advanced Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chin-Chou Wang

    2014-01-01

    Full Text Available Background. This study tested the hypothesis that circulating microparticles (MPs are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC. Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1 platelet-derived activated MPs (PDAc-MPs, (2 platelet-derived apoptotic MPs (PDAp-MPs, (3 endothelial-derived activated MPs (EDAc-MPs, and (4 endothelial-derived apoptotic MPs (EDAp-MPs, were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 (n=56 (one-year survivors and patients who survived less than one year were categorized into group 2 (n=51 (one-year nonsurvivors. Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P<0.05. Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 (P=0.006. Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P<0.035. Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.

  12. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  13. Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Borghaei, Hossein; Alpaugh, Katherine; Hedlund, Gunnar

    2009-01-01

    recognizing the tumor-associated antigen 5T4. PATIENTS AND METHODS: Patients with non-small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose...

  14. Hope for progress after 40 years of futility? Novel approaches in the treatment of advanced stage III and IV non-small-cell-lung cancer: Stereotactic body radiation therapy, mediastinal lymphadenectomy, and novel systemic therapy

    Directory of Open Access Journals (Sweden)

    Simon Fung Kee Fung

    2012-01-01

    Full Text Available Non-small-cell lung cancer (NSCLC remains a leading cause of cancer mortality. The majority of patients present with advanced (stage III-IV disease. Such patients are treated with a variety of therapies including surgery, radiation, and chemotherapy. Despite decades of work, however, overall survival in this group has been resistant to any substantial improvement. This review briefly details the evolution to the current standard of care for advanced NSCLC, advances in systemic therapy, and novel techniques (stereotactic body radiation therapy [SBRT], and transcervical extended mediastinal lymphadenectomy [TEMLA] or video-assisted mediastinal lymphadenectomy [VAMLA] that have been used in localized NSCLC. The utility of these techniques in advanced stage therapy and potential methods of combining these novel techniques with systemic therapy to improve survival are discussed.

  15. Tracking the Evolution of Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Jamal-Hanjani, Mariam; Wilson, Gareth A.; McGranahan, Nicholas

    2017-01-01

    Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine...... as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .)....

  16. Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Schaefer, Eric S; Baik, Christina

    2016-01-01

    Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%–7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg

  17. Role of [{sup 18}F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Caicedo, Carlos; Garcia-Velloso, Maria Jose; Vigil Diaz, Carmen; Richter Echevarria, Jose Angel [University of Navarra, Nuclear Medicine Department, University Clinic of Navarra, Pamplona (Spain); Lozano, Maria Dolores; Labiano, Tania [University of Navarra, Pathology Department, University Clinic of Navarra, Pamplona (Spain); Lopez-Picazo, Jose Maria; Gurpide, Alfonso; Perez Gracia, Jose Luis [University of Navarra, Oncology Department, University Clinic of Navarra, Pamplona (Spain); Zulueta, Javier [University of Navarra, Pulmonology Department, University Clinic of Navarra, Pamplona (Spain)

    2014-11-15

    The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [{sup 18}F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC. Between January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [{sup 18}F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [{sup 18}F]FDG PET/CT for predicting KRAS mutation. From 102 patients staged using [{sup 18}F]FDG PET/CT, 28 (27 %) had KRAS mutation (KRAS+), 22 (22 %) had EGFR mutation (EGFR+) and 52 (51 %) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [{sup 18}F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p < 0.001). No significant differences were observed in [{sup 18}F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (p < 0.001). The multivariate analysis showed a sensitivity and specificity of 78.6 % and 62.2 %, respectively, and the AUC was 0.773. NSCLC patients with tumours harbouring KRAS mutations showed significantly higher [{sup 18}F]FDG uptake than WT patients, as assessed in terms of SUVpeak, SUVmax and SUVmean. A multivariate model based on age, gender, AJCC stage and SUVmean might be used as a predictive marker of KRAS mutation status in patients with stage III or IV NSCLC. (orig.)

  18. Effect of change in symptoms, respiratory status, nutritional profile and quality of life on response to treatment for advanced non-small cell lung cancer.

    Science.gov (United States)

    Mohan, Anant; Singh, P; Kumar, S; Mohan, C; Pathak, A K; Pandey, R M; Guleria, R

    2008-01-01

    Quality of life (QOL), and pulmonary and nutritional parameters are important outcome measures during treatment of lung cancer; however, the effect of chemotherapy on these factors and their relationship with clinical response is unclear. Patients with non-small cell lung cancer (NSCLC) were evaluated for symptom profile, nutritional status (using anthropometry), pulmonary functions by spirometry and six minute walk distance (6 MWD), and QOL using the WHO-QOL Bref 26 questionnaire, before and after chemotherapy. Forty-four patients were studied (mean (SD) age, 55 (10) years, 75% males). The majority (98%) had stage III or IV disease and 72% were current / ex-smokers with median pack-years of 27.0 (range, 0.5-90). Some 61% had a Karnofsky Performance Scale (KPS) 70 or 80. The commonest symptoms were coughing, dyspnea, chest pain, anorexia and fever (79%, 72%, 68%, 57% and 40%, respectively). The mean (SD) 6 MWD was 322.5 (132.6) meters. The mean (SD) percentage forced vital capacity (FVC %), and forced expiratory volume in one second (FEV1 %) were 64.7 (18.8) and 57.8 (19.4), respectively. The mean (SD) QOL scores for the physical, psychological, social, and environmental domains were 52.9 (20.5), 56.1 (17.9), 64.5 (21.8), 57.1 (16.6), respectively. Fourteen patients (32%) responded to chemotherapy. Non-responders had significantly higher baseline occurrence of fever, anorexia, and weight loss, higher pack-years of smoking and poorer KPS compared to responders. Overall, chemotherapy caused significant decline in the frequency of coughing, dyspnea, chest pain, fever, anorexia, weight loss, and improvement in hemoglobin and albumin levels. There was no significant improvement in pulmonary functions, nutritional status, or QOL scores after treatment. Lung cancer patients have a poor QOL. Although chemotherapy provides significant symptomatic benefit, this does not translate into similar benefit in respiratory and nutritional status or QOL. Patients with constitutional

  19. Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Topkan, Erkan; Parlak, Cem; Topuk, Savas; Pehlivan, Berrin

    2012-01-01

    Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation. Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively. In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss

  20. Reliability of using circulating tumor cells for detecting epidermal growth factor receptor mutation status in advanced non-small-cell lung cancer patients: a meta-analysis and systematic review

    Directory of Open Access Journals (Sweden)

    Hu F

    2018-03-01

    Full Text Available Fang Hu,* Xiaowei Mao,* Yujun Zhang, Xiaoxuan Zheng, Ping Gu, Huimin Wang, Xueyan ZhangDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC patients.Methods: We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve and area under the summary receiver operating characteristic curve.Results: Eight eligible publications with 255 advanced NSCLC patients were included in this meta-analysis. Taking tumor tissues as reference, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating tumor cells for detecting the epidermal growth factor receptor mutation status were found to be 0.82 (95% confidence interval [CI]: 0.50–0.95, 0.95 (95% CI: 0.24–1.00, 16.81 (95% CI: 0.33–848.62, 0.19 (95% CI: 0.06–0.64, and 86.81 (95% CI: 1.22–6,154.15, respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89–0.94. The subgroup analysis showed that the factors of blood volume, histological type, EGFR-tyrosine kinase inhibitor therapy, and circulating tumor cell and tissue test methods for EGFR accounted for the significant difference of the pooled specificity. No significant difference was found between the pooled sensitivity of the subgroup.Conclusion: Our meta-analysis confirmed that circulating tumor cells are a good surrogate for

  1. Cetuximab and biomarkers in non-small-cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Patil N

    2012-07-01

    Full Text Available Nitin Patil, Mohammed Abba, Heike AllgayerDepartment of Experimental Surgery, Medical Faculty Mannheim, University of Heidelberg and Molecular Oncology of Solid Tumors Unit, German Cancer Research Center (DKFZ, Heidelberg, GermanyAbstract: Cancer progression is a highly complex process that is driven by a constellation of deregulated signaling pathways and key molecular events. In non-small-cell lung cancer (NSCLC, as in several other cancer types, the epidermal growth factor receptor (EGFR and its downstream signaling components represent a key axis that has been found not only to trigger cancer progression but also to support advanced disease leading to metastasis. Two major therapeutic approaches comprising monoclonal antibodies and small molecule tyrosine kinase inhibitors have so far been used to target this pathway, with a combination of positive, negative, and inconsequential results, as judged by patient survival indices. Since these drugs are expensive and not all patients derive benefits from taking them, it has become both pertinent and paramount to identify biomarkers that can predict not only beneficial response but also resistance. This review focuses on the chimeric monoclonal antibody, cetuximab, its application in the treatment of NSCLC, and the biomarkers that may guide its use in the clinical setting. A special emphasis is placed on the EGFR, including its structural and mechanistic attributes.Keywords: NSCLC, cetuximab, biomarker, cancer progression

  2. Cetuximab for treating non-small cell lung cancer.

    Science.gov (United States)

    Mazzarella, Luca; Guida, Alessandro; Curigliano, Giuseppe

    2018-04-01

    Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders. Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers. Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.

  3. Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

    Science.gov (United States)

    Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

    2015-07-01

    Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence

  4. Influence of the number and interval of treatment cycles on cytokine-induced killer cells and their adjuvant therapeutic effects in advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Gu, Yuanlong; Lv, Huimin; Zhao, Juan; Li, Qi; Mu, Guannan; Li, Jiade; Wuyang, Jiazi; Lou, Ge; Wang, Ruitao; Zhang, Yanqiao; Huang, Xiaoyi

    2017-09-01

    Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry. After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P=0.0189 and P=0.0129, respectively). The median OS of the ACT≥4cycles subgroup was significantly longer than that of the ACTcells in patients who received ≥4cycles of ACT was higher than that in patients treated with cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells. Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC. Copyright © 2017. Published by Elsevier B.V.

  5. Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study

    OpenAIRE

    Morrow, C. J.; Trapani, F.; Metcalf, R. L.; Bertolini, G.; Hodgkinson, C. L.; Khandelwal, G.; Kelly, P.; Galvin, M.; Carter, L.; Simpson, K. L.; Williamson, S.; Wirth, C.; Simms, N.; Frankliln, L.; Frese, K. K.

    2016-01-01

    Background Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, ?liquid biopsies? such as circulating tumour cells (CTCs) are minimally invasive...

  6. Approach for oligometastasis in non-small cell lung cancer.

    Science.gov (United States)

    Suzuki, Hidemi; Yoshino, Ichiro

    2016-04-01

    Non-small cell lung cancer (NSCLC) harboring a limited number of distant metastases, referred to as the oligometastatic state, has been indicated for surgery for the past several decades. However, whether the strategy of surgical treatment results in a survival benefit for such patients remains controversial. Experientially, however, thoracic surgeons often encounter long-term survivors among surgically resected oligometastatic NSCLC patients. In this article, the current situation of surgical approach and potential future perspective for oligometastatic NSCLC are reviewed.

  7. Treatment of Stage IV Non-small Cell Lung Cancer

    Science.gov (United States)

    Evans, Tracey; Gettinger, Scott; Hensing, Thomas A.; VanDam Sequist, Lecia; Ireland, Belinda; Stinchcombe, Thomas E.

    2013-01-01

    Background: Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. Methods: A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. Results: The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second- and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Conclusions: Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the

  8. Feasibility of [18F]FDG-PET and coregistered CT on clinical target volume definition of advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Messa, C.; IBFM-CNR, Milan; Scientific Institute H.S. Raffaele, Milan; Ceresoli, G.L.; Gregorc, V.; Rizzo, G.; Scientific Institute H.S. Raffaele, Milan; Artioli, D.; Cattaneo, M.; Castellone, P.; Picchio, M.; Landoni, C.; Scientific Institute H.S. Raffaele, Milan; Fazio, F.; IBFM-CNR, Milan; Scientific Institute H.S. Raffaele, Milan; Scientific Institute H.S. Raffaele, Milan

    2005-01-01

    Aim. To prospectively evaluate the impact of co registered positron emission tomography (PET) and computed tomography (CT) in 3D conformal radiotherapy (3D-CRT) planning in patients with non-small lung cancer (NSCLC). Methods. Twenty-one patients (median age: 57 years; range: 42-80 years) referred to 3D-CRT for NSCLC were recruited. Positron emission tomography with 18 F-fluorodeoxyglucose ([ 18 F]FDG-PET) and conventional CT images were coregistered (PET/CT images) using a commerciaI software package based on surface matching technique. Neoplastic areas were contoured on [ 18 F]FDGPET images with the aid of the correspondent CT image by a nuclear medicine physician. CT images and their relative PET contours were then transferred to treatment planning system. A radiation oncologist firstly contoured clinical target volumes (CTV) on CT scan alone (CTV-CT), and then on co registered PET/CT images (CTV-PET/CT). CTV-CT and CTV-PET/CT were compared for each patient; a difference higher than 25% was considered of clinical relevance. Results. Three patients were shifted to palliative radiotherapy for metastatic disease or very large tumor size, showed by [ 18 F]FDG-PET. Of the remaining 18 patients a CTV change, after inclusion of PET/CT data, was observed in 10/18 cases (55%): larger in 7/18 (range 33-279%) and smaller in 3/18 patients (range 26-34%), mainly due to inclusion or exclusion of Iymph-nodal disease and to better definition of tumor extent. CTV changes smaller than 25% occurred in the remaining 8/18 patients. Conclusion. [ 18 F]FDG-PET and CT images co-registration in radiotherapy treatment planning Ied to a change in CTV definition in the majority of our patients, which may signillcantly modify management and radiation treatment modality in these patients

  9. Phase I/II Trial of Sequential Chemoradiotherapy Using a Novel Hypoxic Cell Radiosensitizer, Doranidazole (PR-350), in Patients With Locally Advanced Non-Small-Cell Lung Cancer (WJTOG-0002)

    International Nuclear Information System (INIS)

    Nishimura, Yasumasa; Nakagawa, Kazuhiko; Takeda, Koji; Tanaka, Masahiro; Segawa, Yoshihiko; Tsujino, Kayoko; Negoro, Shunichi; Fuwa, Nobukazu; Hida, Toyoaki; Kawahara, Masaaki; Katakami, Nobuyuki; Hirokawa, Keiko; Yamamoto, Nobuyuki; Fukuoka, Masahiro; Ariyoshi, Yutaka

    2007-01-01

    Purpose: This Phase I/II trial was conducted to assess the efficacy and safety of PR-350, a novel hypoxic cell radiosensitizer, when administered with thoracic radiation therapy (RT) after induction chemotherapy (CT) for locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Two cycles of cisplatin (80 mg/m 2 ) and paclitaxel (180 mg/m 2 ), or carboplatin (AUC = 6) and paclitaxel (200 mg/m 2 ) were given before RT of 60 Gy in 30 fractions. In the Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000 mg/m 2 ) in combination with RT, and this number was increased in increments of 10 for successive groups to 30 doses. Results: In total, 37 patients were enrolled. In Phase I (n = 20), PR-350 could be administered 30 times with concurrent thoracic RT. Thus, in Phase II (n = 17), PR-350 was administered 30 times. The major toxicity was radiation pneumonitis, with Grade 3 or more pneumonitis noted in 6 patients (16%) including 2 with treatment-related deaths. However, no Grade 3 or more esophageal toxicity was noted, and only Grade 1 peripheral neuropathy was noted in 9 patients (24%). For all 37 patients, the median survival time (MST) and the 2-year survival rate were 15.9 months and 24%, respectively. For 18 patients receiving 21 to 30 doses of PR-350, the MST and 2-year survival rate were 20.9 months and 33%, respectively. Conclusions: Thoracic RT combined with 30 daily administrations of PR-350 after induction CT was well tolerated and promising for locally advanced NSCLC

  10. A Meta-Analysis of Changes and Determinants of Quality of Life in Advanced Non-Small Cell Lung Cancer Patients undergoing Chemotherapy

    Directory of Open Access Journals (Sweden)

    Yu-Lee Dai

    2015-09-01

    The findings of this meta-analysis and systematic review suggest that by appropriately managing high-risk NSCLC patients’ symptom distress, alleviating their anxiety and depressive symptoms, and enhancing their social support, health care professionals can improve the QOL of advanced NSCLC patients undergoing chemotherapy.

  11. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial

    Science.gov (United States)

    Rizvi, Naiyer A; Mazières, Julien; Planchard, David; Stinchcombe, Thomas E; Dy, Grace K; Antonia, Scott J; Horn, Leora; Lena, Hervé; Minenza, Elisa; Mennecier, Bertrand; Otterson, Gregory A; Campos, Luis T; Gandara, David R; Levy, Benjamin P; Nair, Suresh G; Zalcman, Gérard; Wolf, Jürgen; Souquet, Pierre-Jean; Baldini, Editta; Cappuzzo, Federico; Chouaid, Christos; Dowlati, Afshin; Sanborn, Rachel; Lopez-Chavez, Ariel; Grohe, Christian; Huber, Rudolf M; Harbison, Christopher T; Baudelet, Christine; Lestini, Brian J; Ramalingam, Suresh S

    2015-01-01

    Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in

  12. Evaluation of the Reliability of Electronic Medical Record Data in Identifying Comorbid Conditions among Patients with Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Muehlenbein, C. E.; Lawson, A.; Pohl, G.; Hoverman, R.; Gruschkus, S. K.; Forsyth, M.; Chen, C.; Lopez, W.; Hartnett, H. J.

    2011-01-01

    Traditional methods for identifying co morbidity data in EMRs have relied primarily on costly and time-consuming manual chart review. The purpose of this study was to validate a strategy of electronically searching EMR data to identify co morbidities among cancer patients. Methods. Advanced stage NSCLC patients ( N = 2,513) who received chemotherapy from 7/1/2006 to 6/30/2008 were identified using iKnowMed, US Oncology's proprietary oncology-specific EMR system. EMR data were searched for documentation of co morbidities common to advanced stage cancer patients. The search was conducted by a series of programmatic queries on standardized information including concomitant illnesses, patient history, review of systems, and diagnoses other than cancer. The validity of the co morbidity information that we derived from the EMR search was compared to the chart review gold standard in a random sample of 450 patients for whom the EMR search yielded no indication of co morbidities. Negative predictive values were calculated. Results. The overall prevalence of co morbidities of 22%. Overall negative predictive value was 0.92 in the 450 patients randomly sampled patients (36 of 450 were found to have evidence of co morbidities on chart review). Conclusion. Results of this study suggest that efficient queries/text searches of EMR data may provide reliable data on co morbid conditions among cancer patients.

  13. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Scagliotti, G.V.; Parikh, P.; Pawel, J. von

    2008-01-01

    , in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/ gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ... neutropenia (P = .002); and alopecia (P

  14. Mathematical modeling for Phase I cancer trials: A study of metronomic vinorelbine for advanced non-small cell lung cancer (NSCLC) and mesothelioma patients.

    Science.gov (United States)

    Barlesi, Fabrice; Imbs, Diane-Charlotte; Tomasini, Pascale; Greillier, Laurent; Galloux, Melissa; Testot-Ferry, Albane; Garcia, Mélanie; Elharrar, Xavier; Pelletier, Annick; André, Nicolas; Mascaux, Céline; Lacarelle, Bruno; Cheikh, Raouf El; Serre, Raphaël; Ciccolini, Joseph; Barbolosi, Dominique

    2017-07-18

    Using mathematical modelling allows to select a treatment's regimen across infinite possibilities. Here, we report the phase I assessment of a new schedule for metronomic vinorelbine in treating refractory advanced NSCLC and mesothelioma patients. Overall, 13 patients were screened and 12 were treated (50% male, median age: 68yrs), including 9 NSCLC patients. All patients received at least one week (3 doses) of treatment. At data cut-off, the median length of treatment was 6.5 weeks (1-32+). All the patients presented with at least one adverse event (AE) and six patients with a severe AE (SAE). One partial response and 5 stable diseases were observed. The median OS was 6.4 months (95% CI, 4.8 to 12 months). The median and mean vinorelbine's AUC were 122 ng/ml*h and 159 ng/ml*h, respectively, with the higher plasmatic vinorelbine exposure associated with the best ORR (difference of AUC comparison between responders and non-responders, p-value 0.017). The mathematical modelling determined the administration of vinorelbine, 60 mg on Day 1, 30 mg on Day 2 and 60 mg on Day 4 weekly until progression, as the best schedule. Advanced NSCLC or mesothelioma patients progressing after standard treatment were eligible for the trial. NCT02555007. Responses with acceptable safety profile were observed in heavily pretreated NSCLC and mesothelioma patients using oral vinorelbine at this metronomic dosage based on a mathematic modeling. This study demonstrates the feasibility of this new type of approach, as mathematical modeling may help to rationally decide the better regimen to be clinically tested across infinite possibilities.

  15. Serum tumor markers CEA, CYFRA21-1, and CA-125 are associated with worse prognosis in advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Cedrés, Susana; Nuñez, Isaac; Longo, Marina; Martinez, Pablo; Checa, Eva; Torrejón, Davis; Felip, Enriqueta

    2011-05-01

    Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC. Two hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases. Baseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Our Experiences with Erlotinib in Second and Third Line Treatment Patients with Advanced Stage Iiib/ Iv Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Bakir Mehić

    2008-11-01

    Full Text Available HeadHER1/EGFR is known to play a pivotal role in tumorigenesis and is overexpressed in up to 80% of NSCLCs. The study of an Expanded Access Clinical Program of Erlotinib in NSCLC is a phase IV openlabel, non-randomized, multicenter trial in patients with advanced (inoperable stage IIIb/IV NSCLC who were eligible for treatment with erlotinib but had no access to trial participation. Patients for the study from Bosnia and Herzegovina (B&H were selected from two Clinical centres (Sarajevo and Banja Luka. The aim of study was to evaluated efficacy and tolerability of erlotinib monotherapy in this setting. All patients who received at least one dose of erlotinib and data were entered in the database as of the CRF cut-off date of 14th May 2008 were included in analysis of data (n = 19. This population is defined as the Intent to Treat (ITT population and includes all patients who had at least one dose of erlotinib regardless of whether major protocol violations were incurred. The findings are consistent with the results of the randomized, placebo-controlled BR.21 study. Indicating that erlotinib is an effective option for patients with advanced NSCLC who are unsuitable for, or who have previously failed standard chemotherapy. In B&H group of patients DCR was almost 84%, and PFS was approximately 24,7 weeks (compared with 44% and 9,7 weeks for erlotinib reported in phase III. Almost three quarter of the patients received erlotinib as their second line of therapy. Overall, erlotinib was well tolerated; there were no patients who withdrew due to a treatment-related AE (mainly rash and there were few dose reductions. 24% of patients experienced an SAE (most commonly gastrointestinal (GI disorders.

  17. Molecular Epidemiology of EGFR Mutations in Asian Patients with Advanced Non-Small-Cell Lung Cancer of Adenocarcinoma Histology – Mainland China Subset Analysis of the PIONEER study

    Science.gov (United States)

    Shi, Yuankai; Li, Junling; Zhang, Shucai; Wang, Mengzhao; Yang, Shujun; Li, Ning; Wu, Gang; Liu, Wei; Liao, Guoqing; Cai, Kaican; Chen, Liang’an; Zheng, Meizhen; Yu, Ping; Wang, Xiuwen; Liu, Yunpeng; Guo, Qisen; Nie, Ligong; Liu, Jiwei; Han, Xiaohong

    2015-01-01

    Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naïve lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naïve) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0–10 pack-year, OR 0.27, 95%CI: 0.17–0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29–0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged. PMID:26599344

  18. SU-F-J-64: Comparison of Dosimetric Robustness Between Proton Therapy and IMRT Plans Following Tumor Regression for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Teng, C; Ainsley, C; Teo, B; Burgdorf, B; Berman, A; Levin, W; Xiao, Y; Lin, L; Simone, C; Solberg, T [University of Pennsylvania, Philadelphia, PA (United States); Janssens, G [IBA, Louvain-la-Neuve (Belgium)

    2016-06-15

    Purpose: In the light of tumor regression and normal tissue changes, dose distributions can deviate undesirably from what was planned. As a consequence, replanning is sometimes necessary during treatment to ensure continued tumor coverage or to avoid overdosing organs at risk (OARs). Proton plans are generally thought to be less robust than photon plans because of the proton beam’s higher sensitivity to changes in tissue composition, suggesting also a higher likely replanning rate due to tumor regression. The purpose of this study is to compare dosimetric deviations between forward-calculated double scattering (DS) proton plans with IMRT plans upon tumor regression, and assesses their impact on clinical replanning decisions. Methods: Ten consecutive locally advanced NSCLC patients whose tumors shrank > 50% in volume and who received four or more CT scans during radiotherapy were analyzed. All the patients received proton radiotherapy (6660 cGy, 180 cGy/fx). Dosimetric robustness during therapy was characterized by changes in the planning objective metrics as well as by point-by-point root-mean-squared differences for the entire PTV, ITV, and OARs (heart, cord, esophagus, brachial plexus and lungs) DVHs. Results: Sixty-four pairs of DVHs were reviewed by three clinicians, who requested a replanning rate of 16.7% and 18.6% for DS and IMRT plans, respectively, with a high agreement between providers. Robustness of clinical indicators was found to depend on the beam orientation and dose level on the DVH curve. Proton dose increased most in OARs distal to the PTV along the beam path, but these changes were primarily in the mid to low dose levels. In contrast, the variation in IMRT plans occurred primarily in the high dose region. Conclusion: Robustness of clinical indicators depends where on the DVH curves comparisons are made. Similar replanning rates were observed for DS and IMRT plans upon large tumor regression.

  19. Regional immunotherapy has a detrimental effect on the response to combined irradiation and chemotherapy in locally advanced non-small cell bronchognic carcinoma

    International Nuclear Information System (INIS)

    Ruckdeschel, J.C.; De Vore, C.; Caradonna, R.; Horton, J.; McKneally, M.F.; Kellar, S.; McIlduff, J.B.; Baxter, D.H.; Killam, D.; Sedransk, N.

    1981-01-01

    Twenty-one patients with stage III M 0 non-oat cell bronchogenic carcinoma confined to the thorax were randomized to receive either intrapleural BCG (10 7 cfu, Tice strain) or intrapleural saline 3 weeks prior to beginning combined irradiation and chemotherapy. Radiation to the primary tumor and regional nodes was given at a dose of 3,000 rad in ten sessions and was followed in 7-14 days by CAMP chemotherapy (cyclophosphamide, adriamycin, methotrexate, and procarbazine) for a planned duration of 6 months. Isoniazid, 300 mg/day, was given to all patients for 3 months starting 1 week after intrapleural therapy. There were no significant differences in pretreatment prognostic factors or in response to radiation therapy. The patients receiving intrapleural BCG in addition to radiation and chemotherapy had a median survival of 18 weeks, significantly shorter than that for the patients receiving intrapleural saline (54 weeks, P=0.017). (orig.)

  20. A Competing Risk Model of First Failure Site after Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Nygård, Lotte; Vogelius, Ivan R; Fischer, Barbara M; Kjær, Andreas; Langer, Seppo W; Aznar, Marianne C; Persson, Gitte F; Bentzen, Søren M

    2018-04-01

    The aim of the study was to build a model of first failure site- and lesion-specific failure probability after definitive chemoradiotherapy for inoperable NSCLC. We retrospectively analyzed 251 patients receiving definitive chemoradiotherapy for NSCLC at a single institution between 2009 and 2015. All patients were scanned by fludeoxyglucose positron emission tomography/computed tomography for radiotherapy planning. Clinical patient data and fludeoxyglucose positron emission tomography standardized uptake values from primary tumor and nodal lesions were analyzed by using multivariate cause-specific Cox regression. In patients experiencing locoregional failure, multivariable logistic regression was applied to assess risk of each lesion being the first site of failure. The two models were used in combination to predict probability of lesion failure accounting for competing events. Adenocarcinoma had a lower hazard ratio (HR) of locoregional failure than squamous cell carcinoma (HR = 0.45, 95% confidence interval [CI]: 0.26-0.76, p = 0.003). Distant failures were more common in the adenocarcinoma group (HR = 2.21, 95% CI: 1.41-3.48, p failure showed that primary tumors were more likely to fail than lymph nodes (OR = 12.8, 95% CI: 5.10-32.17, p failure (OR = 1.26 per unit increase, 95% CI: 1.12-1.40, p failure site-specific competing risk model based on patient- and lesion-level characteristics. Failure patterns differed between adenocarcinoma and squamous cell carcinoma, illustrating the limitation of aggregating them into NSCLC. Failure site-specific models add complementary information to conventional prognostic models. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  1. Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Bonnet, R.; Presselt, N.; Przetak, C.; Junker, K.; Schneider, C.P.; Hoeffken, K.; Wendt, T.G.

    2002-01-01

    Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m 2 ) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m 2 ) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

  2. ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia.

    Science.gov (United States)

    Currow, D; Temel, J S; Abernethy, A; Milanowski, J; Friend, J; Fearon, K C

    2017-08-01

    Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities. ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ≤2 after completing 12 weeks (w) on the ROMANA 1 or ROMANA 2 trials (0-12 weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100 mg or placebo once daily for an additional 12w (12-24 weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12-24 weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0-24 weeks). Of the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N = 345, mean age 62.0 years; placebo, N = 168; mean age 62.2 years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment-emergent adverse events (TEAEs; 52.2% versus 55.7%), grade ≥3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia-cachexia symptoms observed in the original trials were consistently maintained over 12-24 weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P < 0.05). No significant improvement in HGS was seen in either group. During the 12-24 weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0-24w treatment period, body weight and symptom burden were improved

  3. Comparison of single-agent chemotherapy and targeted therapy to first-line treatment in patients aged 80 years and older with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhang QQ

    2015-04-01

    Full Text Available Qianqian Zhang,1 Zhehai Wang,2 Jun Guo,2 Liyan Liu,2 Xiao Han,2 Minmin Li,1 Shu Fang,1 Xiang Bi,1 Ning Tang,1 Yang Liu1 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, 2Department of Oncology, Shandong Cancer Hospital, Jinan, People’s Republic of China Purpose: The aim of this study was to compare single-agent chemotherapy with targeted therapy in initial treatment and to explore a better choice of treatment for patients aged 80 years and older with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A retrospective chart review was conducted for 136 patients aged 80 years and older who were cytopathologically diagnosed and staged as advanced (stage IIIB or IV NSCLC. The patient population was divided into two treatment groups: 78 patients were allocated to the chemotherapy group (group A, pemetrexed or gemcitabine or docetaxel as a single agent, and 60 patients were allocated to another group and received epidermal growth factor-receptor tyrosine-kinase inhibitors (group B, erlotinib or gefitinib as a single agent. The primary end points were overall survival (OS and progression-free survival (PFS, and the secondary end points were response rate, disease-control rate, safety, and quality of life.Results: In group A and group B, respectively, the median PFS was 2 versus 4 months (P=0.013, and the median OS was 8 versus 16 months (P=0.025. The 1- and 2-year survival rates of the two groups were 23.7% (group A, 18 of 76 versus 76.7% (group B, 46 of 60 and 13.2% (group A, ten of 76 versus 10% (group B, six of 60, respectively. The response rate and disease-control rate were 28.9% versus 36.7% (P=0.39 and 57.9% versus 76.7% (P=0.022 in group A and group B, respectively.Conclusion: Elders aged 80 years and over with advanced NSCLC in group B had longer PFS and OS compared with group A. It was well tolerated in group B because of the mild adverse effects. Targeted therapy can be

  4. Comparative effectiveness and safety of nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin in first-line treatment of advanced squamous cell non-small cell lung cancer in a US community oncology setting

    Directory of Open Access Journals (Sweden)

    Mudad R

    2017-10-01

    Full Text Available Raja Mudad,1 Manish B Patel,2 Sandra Margunato-Debay,2 David Garofalo,3 Lincy S Lal4 1University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Hollywood, FL, USA; 2Celgene Corporation, Summit, NJ, USA; 3Cardinal Health, Dallas, TX, USA; 4University of Texas School of Public Health, Houston, TX, USA Introduction: Real-world comparative effectiveness, safety, and supportive care use of nab-paclitaxel plus carboplatin vs gemcitabine plus platinum were analyzed in patients with advanced or metastatic squamous cell non-small cell lung cancer (NSCLC.Materials and methods: Patients who received ≥ 1 cycle of first-line nab-paclitaxel plus carboplatin or gemcitabine plus platinum were identified from the Navigating Cancer database. Clinical effectiveness endpoints included overall survival (OS and time to treatment discontinuation (TTD. Other endpoints included safety and utilization of supportive care. Cox proportional hazards models were used to control for potential confounding effects of baseline characteristics.Results: In total, 193 patients were included (nab-paclitaxel plus carboplatin, n = 61; gemcitabine plus platinum, n = 132. Baseline characteristics were generally similar between the cohorts. Patients receiving nab-paclitaxel plus carboplatin had a significantly longer OS than those receiving gemcitabine plus carboplatin (median, 12.8 vs 9.0 months; P = 0.03. However, the adjusted difference was not statistically significant (adjusted HR 1.55; 95% CI, 0.99–2.42; P = 0.06. nab-Paclitaxel plus carboplatin-treated patients had significantly longer TTD than gemcitabine plus carboplatin-treated patients (median, 4.3 vs 3.5 months; P = 0.03; adjusted HR 1.39; 95% CI, 1.01–1.90; P = 0.04. Grade 3 or 4 anemia and neutropenia were significantly lower in patients treated with nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin. Nausea and neuropathy (grade not specified were significantly higher in the

  5. Management of non-small cell lung cancer with oligometastasis.

    Science.gov (United States)

    Villaruz, Liza C; Kubicek, Gregory J; Socinski, Mark A

    2012-08-01

    Patients with oligometastatic Non-Small Cell Lung Cancer (NSCLC) present a potential opportunity for curative therapy; however, the challenge remains the definitive treatment of their localized disease and ablation of their limited overt metastatic sites of disease. In selecting patients with oligometastatic NSCLC for definitive therapy, proper staging through radiographic studies, including PET and brain MRI, and the pathologic staging of the mediastinal lymph nodes and potential sites of metastatic disease, are critical. With that in mind, the available literature suggests that in highly selected patients with solitary metastases to the brain, adrenals and other organs, long term survival may be achieved with combined definitive therapy of both the primary lung tumor and the solitary metastatic site.

  6. A phase III comparison of radiation therapy with or without recombinant β-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04)

    International Nuclear Information System (INIS)

    Bradley, Jeffrey D.; Scott, Charles B.; Paris, Kristie J.; Demas, William F.; Machtay, Mitchell; Komaki, Ritsuko; Movsas, Benjamin; Rubin, Philip; Sause, William T.

    2002-01-01

    acute toxicities were primarily related to lung (n=8) and esophagus (n=7). No Grade 4 or 5 late toxicities were seen for patients in the radiation-alone arm. However, three patients on the β-interferon arm experienced Grade 4 toxicity, and one patient died. The 1-year survival rate for the RT-alone arm was 44% with a median survival time of 9.5 months. The 1-year survival on the β-interferon arm was 42% with a median survival of 10.3 months. There was no statistical difference in survival times (p=0.66). Conclusions: This multicenter, controlled Phase III trial failed to confirm the efficacy of Betaseron in patients receiving definitive radiotherapy for locally advanced, nonmetastatic non-small-cell lung cancer. The use of β-interferon led to greater rates of both acute and late treatment-related toxicity. The RTOG continues to investigate other biologic modifiers that may provide a nontoxic alternative for this poor-risk population

  7. Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials.

    Science.gov (United States)

    Zhang, Yaxiong; Zhang, Zhonghan; Huang, Xiaodan; Kang, Shiyang; Chen, Gang; Wu, Manli; Miao, Siyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2017-09-01

    Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments. Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate. Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib). Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Cost-effectiveness of continuation maintenance pemetrexed after cisplatin and pemetrexed chemotherapy for advanced nonsquamous non-small-cell lung cancer: estimates from the perspective of the Chinese health care system.

    Science.gov (United States)

    Zeng, Xiaohui; Peng, Liubao; Li, Jianhe; Chen, Gannong; Tan, Chongqing; Wang, Siying; Wan, Xiaomin; Ouyang, Lihui; Zhao, Ziying

    2013-01-01

    Continuation maintenance treatment with pemetrexed is approved by current clinical guidelines as a category 2A recommendation after induction therapy with cisplatin and pemetrexed chemotherapy (CP strategy) for patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). However, the cost-effectiveness of the treatment remains unclear. We completed a trial-based assessment, from the perspective of the Chinese health care system, of the cost-effectiveness of maintenance pemetrexed treatment after a CP strategy for patients with advanced nonsquamous NSCLC. A Markov model was developed to estimate costs and benefits. It was based on a clinical trial that compared continuation maintenance pemetrexed therapy plus best supportive care (BSC) versus placebo plus BSC after a CP strategy for advanced nonsquamous NSCLC. Sensitivity analyses were conducted to assess the stability of the model. The model base case analysis suggested that continuation maintenance pemetrexed therapy after a CP strategy would increase benefits in a 1-, 2-, 5-, or 10-year time horizon, with incremental costs of $183,589.06, $126,353.16, $124,766.68, and $124,793.12 per quality-adjusted life-year gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was the utility of the progression-free survival state, followed by proportion of patients with postdiscontinuation therapy in both arms, proportion of BSC costs for PFS versus progressed survival state, and cost of pemetrexed. Probabilistic sensitivity analysis indicated that the cost-effective probability of adding continuation maintenance pemetrexed therapy to BSC was zero. One-way and probabilistic sensitivity analyses revealed that the Markov model was robust. Continuation maintenance of pemetrexed after a CP strategy for patients with advanced nonsquamous NSCLC is not cost-effective based on a recent clinical trial. Decreasing the price or adjusting the dosage of pemetrexed may be a better option

  9. Definitive Upfront Stereotactic Ablative Radiotherapy Combined with Image-Guided, Intensity Modulated Radiotherapy (IG-IMRT or IG-IMRT Alone for Locally Advanced Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Alexander Chi

    Full Text Available Image-guided (IG intensity-modulated radiotherapy (IMRT enables maximal tumor margin reduction for the sparing of organs at risk (OARs when used to treat locally advanced non-small cell lung cancer (NSCLC with definitive chemo-radiation. It also allows for the incorporation of stereotactic ablative radiotherapy (SABR into the treatment regimen. Here, we describe our initial experience in combining definitive upfront SABR to the primary lesion with chemo-radiation delivered with conventionally fractionated IG-IMRT to the remaining regional disease; along with clinical outcome following chemo-radiation with conventionally fractionated IG-IMRT alone in the treatment of locally advanced NSCLC.The clinical outcome of 29 patients with locally advanced NSCLC who underwent conventionally fractionated IG-IMRT, or definitive upfront SABR followed by IG-IMRT combined with chemotherapy (induction, concurrent, or both was retrospectively reviewed.After a median follow up of 23.7 months, the median overall survival (OS and progression-free survival (PFS were 19.8 and 11.3 months, respectively. The 2 year local, regional, and distant control was 60%, 62%, and 38%, respectively. No local failure was observed in 3 patients following SABR + IG-IMRT while 6/26 patients failed locally following IG-IMRT alone. SABR + IG-IMRT was well tolerated. No ≥ grade 3 radiation-related toxicity was observed.Definitive upfront SABR followed by IG-IMRT in selected patients with locally advanced NSCLC warrants further investigation in future clinical trials, while chemo-radiation with IG-IMRT alone was well tolerated.

  10. Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer : a systematic review and cost-effectiveness analysis

    NARCIS (Netherlands)

    Westwood, Marie; Joore, Manuela; Whiting, Penny; van Asselt, Thea; Ramaekers, Bram; Armstrong, Nigel; Misso, Kate; Severens, Johan; Kleijnen, Jos

    BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment with standard chemotherapy.

  11. Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: A systematic review and cost-effectiveness analysis

    NARCIS (Netherlands)

    M. Westwood (Marie); M.A. Joore (Manuela); P. Whiting (Penny); T. van Asselt (Thea); B.L.T. Ramaekers (Bram); N. Armstrong (Nigel); K. Misso (Kate); J.L. Severens (Hans); J. Kleijnen (Jos)

    2014-01-01

    markdownabstract__Abstract__ Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment

  12. Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Joerger, M; von Pawel, J; Kraff, S; Fischer, J R; Eberhardt, W; Gauler, T C; Mueller, L; Reinmuth, N; Reck, M; Kimmich, M; Mayer, F; Kopp, H-G; Behringer, D M; Ko, Y-D; Hilger, R A; Roessler, M; Kloft, C; Henrich, A; Moritz, B; Miller, M C; Salamone, S J; Jaehde, U

    2016-10-01

    Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. The efficacy and safety of standardized allergen-removed Rhus verniciflua extract as maintenance therapy after first-line chemotherapy in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Lee, Jinsoo; Chae, Jean; Lee, Sookyung; Kim, Kyungsuk; Eo, Wankyu; Kim, Sehyun; Choi, Woncheol; Cheon, Seong Ha

    2013-01-01

    Chemotherapy improves the survival of patients with advanced non-small cell lung cancer (NSCLC), but tumor progression is often inevitable. Strategies are needed to improve the therapeutic efficacy of chemotherapy. Over recent years, there has been increasing interest in the role of maintenance therapy after first-line chemotherapy. We investigated the efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract (aRVS) as maintenance therapy in patients with non-progressive disease following first-line chemotherapy. We reviewed the medical records of 33 patients with advanced NSCLC, who started treatment with aRVS in a state of tumor regression or stable disease after completion of four or six cycles of induction chemotherapy at the Integrative Cancer Center, Kyung Hee University Hospital at Gangdong from June 2006 to April 2012. The primary objective of this study was progression-free survival (PFS) of aRVS as maintenance therapy. Secondary objectives included assessments of disease control rate (DCR), overall survival (OS), and the safety of aRVS treatment. The median PFS was 5.2 months with a 6- and 12-month PFS rate of 40.6% and 12.9%, respectively. The DCR was 93.9% and the median OS was 34.8 months. The overall survival rates at 12, 24, and 36 months were 84.2%, 76.7% and 49.9%, respectively. We observed no hematologic toxicity, nephrotoxicity, or hepatotoxicity during aRVS treatment. In conclusion, maintenance therapy with aRVS for patients with advanced NSCLC is well-tolerated and offers encouraging improved PFS and OS compared with historical controls. Our data provide further evidence that aRVS may be used beyond disease progression in this clinical setting.

  14. The Predictive Value of Early In-Treatment 18F-FDG PET/CT Response to Chemotherapy in Combination with Bevacizumab in Advanced Nonsquamous Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Usmanij, Edwin A; Natroshvili, Tinatin; Timmer-Bonte, Johanna N H; Oyen, Wim J G; van der Drift, Miep A; Bussink, Johan; Geus-Oei, Lioe-Fee de

    2017-08-01

    18 F-FDG PET/CT is potentially applicable to predict response to chemotherapy in combination with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Methods: In 25 patients with advanced nonsquamous NSCLC, 18 F-FDG PET/CT was performed before treatment and after 2 wk, at the end of the second week of first cycle carboplatin-paclitaxel and bevacizumab (CPB) treatment. Patients received up to a total of 4 cycles of CPB treatment. Maintenance treatment with bevacizumab monotherapy was continued until progressive disease without significant treatment-related toxicities of first-line treatment. In the case of progressive disease, bevacizumab was combined with erlotinib. SUV corrected for lean body mass (SUL and SUL peak ) were obtained. PERCIST were used for response evaluation. These semiquantitative parameters were correlated with progression-free survival and overall survival (OS). Results: Metabolic response, defined by a significant reduction in SUL peak of 30% or more after 2 wk of CPB, was predictive of progression-free survival and OS. For partial metabolic responders ( n = 19), the median OS was 22.8 mo. One-year and 2-y OS were 79% and 47%, respectively. Nonmetabolic responders ( n = 6) (stable metabolic disease or progressive disease) showed a median OS of 4.4 mo (1-y and 2-y OS was 33% and 0%, respectively) ( P predictive of outcome to first-line chemotherapy with bevacizumab in patients with advanced nonsquamous NSCLC. This enables identification of patients at risk of treatment failure, permitting treatment alternatives such as early switch to a different therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  15. The role of maintenance pemetrexed in the treatment of non-small-cell lung cancer

    OpenAIRE

    Rafii, S

    2010-01-01

    Saeed Rafii, Michael H CullenDepartment of Medical Oncology, Queen Elizabeth Hospital, University Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, United KingdomAbstract: Until recently, the weight of evidence has supported the discontinuation of ­chemotherapy in advanced non-small-cell lung cancer (NSCLC) after 4–6 cycles of induction therapy. This allows patients with limited life expectancy a “treatment holiday.” A minority of cases then go on to r...

  16. Non-Small Cell Carcinoma Biomarker Testing: The Pathologist's Perspective.

    Directory of Open Access Journals (Sweden)

    Elisa eBrega

    2014-07-01

    Full Text Available Biomarker testing has become standard of care for patients diagnosed with non-small cell lung cancer. Although it can be successfully performed in circulating tu-mor cells, at present, the vast majority of investigations are carried out using di-rect tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically signifi-cant, particularly in cases of lung adenocarcinomas (ADC, which in turn, has prompted a new proposal for the histologic classification of such pulmonary neo-plasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist’s role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire pro-cess happens in a timely fashion. Therefore, it is part of the pathologist’s respon-sibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play NSCLC bi-omarker testing, as well as to provide a summarized review of the main NSCLC bi-omarkers of

  17. Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

    Science.gov (United States)

    Kesarwala, Aparna H; Ko, Christine J; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E; O'Meara, William P; Simone, Charles B; Rengan, Ramesh

    2015-05-01

    Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT. Published by Elsevier Inc.

  18. Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

    Science.gov (United States)

    Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

    2015-01-01

    Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (pENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all pENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

  19. Involved field radiotherapy (IFRT) versus elective nodal irradiation (ENI) for locally advanced non-small cell lung cancer: a meta-analysis of incidence of elective nodal failure (ENF).

    Science.gov (United States)

    Li, Ruijian; Yu, Liang; Lin, Sixiang; Wang, Lina; Dong, Xin; Yu, Lingxia; Li, Weiyi; Li, Baosheng

    2016-09-21

    The use of involved field radiotherapy (IFRT) has generated concern about the increasing incidence of elective nodal failure (ENF) in contrast to elective nodal irradiation (ENI). This meta-analysis aimed to provide more reliable and up-to-date evidence on the incidence of ENF between IFRT and ENI. We searched three databases for eligible studies where locally advanced non-small cell lung cancer (NSCLC) patients received IFRT or ENI. Outcome of interest was the incidence of ENF. The fixed-effects model was used to pool outcomes across the studies. There were 3 RCTs and 3 cohort studies included with low risk of bias. There was no significant difference in incidence of ENF between IFRT and ENI either among RCTs (RR = 1.38, 95 % CI: 0.59-3.25, p = 0.46) or among cohort studies (RR = 0.99, 95 % CI: 0.46-2.10, p = 0.97). There was also no significant difference in incidence of ENF between IFRT and ENI when RCTs and cohort studies were combined (RR = 1.15, 95 % CI: 0.65-2.01, p = 0.64). I 2 of test for heterogeneity was 0 %. This meta-analysis provides more reliable and stable evidence that there is no significant difference in incidence of ENF between IFRT and ENI.

  20. The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

    Science.gov (United States)

    Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose Javier; Gimenez-Capitan, Ana; Rodriguez, Ignacio; Vergenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

    2013-01-01

    Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy. PMID:24197907

  1. MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer.

    Science.gov (United States)

    Hiura, Kazuya; Shiraishi, Akiko; Suzuki, Chinami; Takamura, Kei; Yamamoto, Makoto; Komori, Hitoshi; Watanabe, Yasuhiro; Iwaki-Egawa, Sachiko

    2015-01-01

    Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. There were no significant differences in these markers levels between groups. However, the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy.

  2. Non small cell carcinoma of the lung: a retrospective study

    International Nuclear Information System (INIS)

    Stevens, G.; Firth, I.

    1992-01-01

    A retrospective study was undertaken in 1990 of 188 patients with the diagnosis of non small cell carcinoma of the lung referred to the Department of Radiation Oncology in 1984. Most patients (178 out of 188) received a course of radiotherapy. This was definitive in 23, palliative in 148 (primary site in 113, metastases in 16, primary plus metastases in 19) and postoperative in 7. This report is a 5 year follow-up of the 171 patients treated by radiation alone, to assess factors that influence survival. Palliative intent of treatment and poorer performance status were related significantly to increasing stage of disease. The effects of palliative treatment were recorded in 79 cases: in 71 there was a reduction in symptoms. The median survival from diagnosis was 8 months. Using univariate and multi-variate analyses, significant and independent prognostic factors for improved survival were good performance status, absence of systemic symptoms, lower tumour stage and curative intent of treatment (higher radiation dose). However the 5-year survival was only 2%. Long-term survival was associated predominantly with early stage disease but not with the type or intent of treatment. Age, sex, histology and apical site did not influence survival. These results are comparable to those found in the literature and emphasize the need to select patients carefully for either palliative or aggressive treatment. 29 refs., 4 tabs., 3 figs

  3. MEK inhibition in non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Johnson, Gary L

    2014-11-01

    KRAS mutations are the most common mutations in non-small cell lung cancer (NSCLC) with adenocarcinoma histology. KRAS mutations result in the activation of the RAF-MEK-ERK pathway, and agents that target RAF-MEK-ERK pathways have been investigated in KRAS mutant NSCLC. The two agents furthest in development are selumetinib and trametinib. Trametinib has greater binding for the MEK1/2 allosteric site, and generally has superior pharmacokinetics. A randomized phase II trial of docetaxel with and without selumetinib revealed that the combination resulted numerically superior overall survival, and a statistically significant improvement in progression-free survival and objective response rate. However, a concerning rate of hospital admission, grade 3 or 4 neutropenia, and febrile neutropenia was observed with the combination. Trials have investigated MEK inhibitors as single agents and in combination with erlotinib, and the data do not support the further development. The activity of MEK inhibitors appears to be similar in patients with KRAS mutant and wild-type NSCLC suggesting KRAS mutation status is not a reliable biomarker for efficacy. It is possible that mutations of genes in addition to KRAS mutations impact the activity of MEK inhibitors, or specific subsets of KRAS mutations may be resistant or susceptible to MEK inhibition. Other potential explanations are gene amplifications, alternative RNA splicing of genes resulting in activation of their protein products, and deregulation of noncoding RNAs and consequent altered protein expression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan SUN

    2015-06-01

    Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

  5. Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH).

    Science.gov (United States)

    Peters, Solange; Gettinger, Scott; Johnson, Melissa L; Jänne, Pasi A; Garassino, Marina C; Christoph, Daniel; Toh, Chee Keong; Rizvi, Naiyer A; Chaft, Jamie E; Carcereny Costa, Enric; Patel, Jyoti D; Chow, Laura Q M; Koczywas, Marianna; Ho, Cheryl; Früh, Martin; van den Heuvel, Michel; Rothenstein, Jeffrey; Reck, Martin; Paz-Ares, Luis; Shepherd, Frances A; Kurata, Takayasu; Li, Zhengrong; Qiu, Jiaheng; Kowanetz, Marcin; Mocci, Simonetta; Shankar, Geetha; Sandler, Alan; Felip, Enriqueta

    2017-08-20

    Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good

  6. Validation and real-world assessment of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung cancer and the cancer anorexia-cachexia syndrome (CACS).

    Science.gov (United States)

    LeBlanc, Thomas W; Samsa, Greg P; Wolf, Steven P; Locke, Susan C; Cella, David F; Abernethy, Amy P

    2015-08-01

    Patients with cancer anorexia-cachexia syndrome (CACS) suffer a significant symptom burden, impaired quality of life (QoL), and shorter survival. Measurement of QoL impairments related to CACS is thereby important both in clinical practice and in research. We aimed to further validate the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) scale in an advanced lung cancer population. We tested the performance of the FAACT and its anorexia-cachexia subscale (ACS) within a dataset of patients with advanced non-small cell lung cancer (aNSCLC), using standard statistical methods. We then compared the performance of commonly used QoL measures stratified by CACS status and by patient self-report of appetite and weight loss. The FAACT and its ACS demonstrate internal validity consistent with acceptable published ranges for other QoL scales (Cronbach alpha = 0.9 and 0.79, respectively). Correlation coefficients demonstrate moderate correlations in the expected directions between FAACT and ACS and scales that measure related constructs. Comparing patients with and without CACS, the ACS is more sensitive to change than other QoL instruments (mean score 33.1 vs. 37.2, p = 0.011, ES = 0.58). In patients with aNSCLC, the FAACT and its ACS performed well compared with other instruments, further supporting their validity and value in clinical research. FAACT and ACS scores covaried with symptoms and other QoL changes that are typical hallmarks of CACS, lending further support to their use as QoL endpoints in clinical trials among patients with CACS.

  7. The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

    Directory of Open Access Journals (Sweden)

    Xingsheng Hu

    Full Text Available Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC previously treated with platinum-based chemotherapy.Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day. The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety.From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m and 5.4 months (95%CI 3.1-7.9 m, respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127, diarrhea (12.6%, 16/127 and elevation of transaminase (15.7%, 20/127.In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy.ClinicalTrials.gov NCT02486354.

  8. The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

    Science.gov (United States)

    Hu, Xingsheng; Zhang, Li; Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

    2015-01-01

    Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m) and 5.4 months (95%CI 3.1-7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. ClinicalTrials.gov NCT02486354.

  9. [Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy 
in the Treatment of Patients with Advanced Non-small Cell Lung Cancer
--A Retrospective Study].

    Science.gov (United States)

    Du, Shuhui; Qin, Da; Pang, Ruiqi; Zhang, Yeqing; Zhao, Siqi; Hu, Mu; Zhi, Xiuyi

    2017-10-20

    Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. "Survival" package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (PRadiofrequency ablation of lung cancer combined with chemotherapy can significantly improve the 2-year survival rate of patients with stage IIIb and stage IV NSCLC.

  10. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057).

    Science.gov (United States)

    Horn, Leora; Spigel, David R; Vokes, Everett E; Holgado, Esther; Ready, Neal; Steins, Martin; Poddubskaya, Elena; Borghaei, Hossein; Felip, Enriqueta; Paz-Ares, Luis; Pluzanski, Adam; Reckamp, Karen L; Burgio, Marco A; Kohlhäeufl, Martin; Waterhouse, David; Barlesi, Fabrice; Antonia, Scott; Arrieta, Oscar; Fayette, Jérôme; Crinò, Lucio; Rizvi, Naiyer; Reck, Martin; Hellmann, Matthew D; Geese, William J; Li, Ang; Blackwood-Chirchir, Anne; Healey, Diane; Brahmer, Julie; Eberhardt, Wilfried E E

    2017-12-10

    Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m 2 every 3 weeks). Minimum follow-up for survival was 24.2 months. Results Two-year overall survival rates with nivolumab versus docetaxel were 23% (95% CI, 16% to 30%) versus 8% (95% CI, 4% to 13%) in squamous NSCLC and 29% (95% CI, 24% to 34%) versus 16% (95% CI, 12% to 20%) in nonsquamous NSCLC; relative reductions in the risk of death with nivolumab versus docetaxel remained similar to those reported in the primary analyses. Durable responses were observed with nivolumab; 10 (37%) of 27 confirmed responders with squamous NSCLC and 19 (34%) of 56 with nonsquamous NSCLC had ongoing responses after 2 years' minimum follow-up. No patient in either docetaxel group had an ongoing response. In the pooled analysis, the relative reduction in the risk of death with nivolumab versus docetaxel was 28% (hazard ratio, 0.72; 95% CI, 0.62 to 0.84), and rates of treatment-related adverse events were lower with nivolumab than with docetaxel (any grade, 68% v 88%; grade 3 to 4, 10% v 55%). Conclusion Nivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC.

  11. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

    Science.gov (United States)

    Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

    2012-10-01

    This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

  12. The superiority of hybrid-volumetric arc therapy (VMAT) technique over double arcs VMAT and 3D-conformal technique in the treatment of locally advanced non-small cell lung cancer – A planning study

    International Nuclear Information System (INIS)

    Chan, Oscar S.H.; Lee, Michael C.H.; Hung, Albert W.M.; Chang, Amy T.Y.; Yeung, Rebecca M.W.; Lee, Anne W.M.

    2011-01-01

    Purpose: To compare the dosimetric performance of three different treatment techniques – conformal radiotherapy (CRT), double arcs volumetric modulated arc therapy (RapidArc, RA) and Hybrid-RapidArc (H-RA) for locally-advanced non-small cell lung cancer (NSCLC). Material and methods: CRT, RA and H-RA plans were optimized for 24 stage III NSCLC patients. The target prescription dose was 60 Gy. CRT consisted of 5–7 coplanar fields, while RA comprised of two 204 o arcs. H-RA referred to two 204 o arcs plus 2 static fields, which accounted for approximately half of the total dose. The plans were optimized to fulfill the departmental plan acceptance criteria. Results: RA and H-RA yielded a 20% better conformity compared with CRT. Lung volume receiving >20 Gy (V20) and mean lung dose (MLD) were the lowest in H-RA (V20 1.7% and 2.1% lower, MLD 0.59 Gy and 0.41 Gy lower than CRT and RA respectively) without jeopardizing the low-dose lung volume (V5). H-RA plans gave the lowest mean maximum spinal cord dose (34.4 Gy, 3.9 Gy < CRT and 2.2 Gy < RA plans) and NTCP of lung. Higher average MU per fraction (addition 52.4 MU) was observed with a reduced treatment time compared with CRT plans. Conclusion: The H-RA technique was superior in dosimetric outcomes for treating locally-advanced NSCLC compared to CRT and RA.

  13. Surgical management of oligometastatic non-small cell lung cancer.

    Science.gov (United States)

    Novoa, Nuria M; Varela, Gonzalo; Jiménez, Marcelo F

    2016-11-01

    The oligometastatic stage IV non-small cell lung cancer (NSCLC) offers a new surgical opportunity. New reported data is showing that surgery can offer a reasonable benefit, in terms of long-term survival, to some patients. The advantages of surgical treatment rely on a more adequate patient selection and a better understanding of the biology of these tumors. Currently, mediastinal involvement of the primary tumor can be identified as the most important prognostic variable after curative-intent of synchronous or metachronous metastasis. It seems clear that the routine use of combined FDG-PET and CT will help to detect the more favorable cohort of oligometastatic patients. As expected, pathological T staging of the primary tumor and the completeness of its resection are also crucial factors influencing final results. The real benefit of the local treatment over synchronous or metachronous metastasis is controversial with series showing better outcomes for metachronous lesions than for synchronous and others offering equal results. Also non conclusive results appear when analyzing different sites of metastasis. Retrospective series tend to show different outcomes depending on the affected organ while usually no differences are found in prospective ones. Most of the current evidence is based on retrospective studies on patients collected along extended periods of time. That represents a great limitation to the knowledge on this topic. Some prospective analyses have added some insight, but still the quality of the evidence is too low to allow drawing robust conclusions. As frequently concluded, prospective well designed investigation is requested to ascertain the value of surgery in this specific population of patients with extended NSCLC.

  14. [Principles of radiotherapy of non-small cell lung cancer].

    Science.gov (United States)

    Esik, Olga; Horváth, Akos; Bajcsay, András; Hideghéty, Katalin; Agócs, László; Pikó, Béla; Lengyel, Zsolt; Petrányi, Agota; Pisch, Julianna

    2002-01-01

    The long-term survival probability for Hungarian lung cancer patients is 10% worse than the best results published in the most highly developed countries (the mean 5-year survival probability in Hungary is 5%, in contrast with the 15% survival probability in the USA). On the basis of the international recommendations and personal experience, an attempt was made to formulate the guidelines for radiotherapy as one of the fundamental non-small cell lung cancer (NSCLC) treatment modalities for national use. An expert panel was set up comprising physicians from 6 radiotherapeutic centers (the National Institute of Oncology / Semmelweis University, Budapest; the Beth Israel Medical Center, New York; the University of Kaposvár; the University of Essen; the University of Debrecen; and the County Hospital of Gyula). Experts in two important medical fields closely related to radiotherapy (surgery and diagnostic imaging) were also engaged in the elaboration of the manuscript. Discussion of the most important principles of the radiotherapy and an overview of the prognostic factors was followed by a critical analysis of the protocols applied in the radiotherapy of Hungarian NSCLC patients during recent decades. The new guidelines suggested for the radiotherapy of NSCLC are presented separately for the postoperative period, marginally resectable tumors, and the aggressive or non-aggressive radiotherapy of inoperable tumors. Detailed accounts are given of the techniques of external irradiation and brachytherapy, and of the acute and late radiation-induced damage of normal tissues. The authors believe that this document may be instrumental in improving the survival index of Hungarian NSCLC patients in the near future.

  15. Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: A systematic review and cost-effectiveness analysis

    OpenAIRE

    Westwood, Marie; Joore, Manuela; Whiting, Penny; Asselt, Thea; Ramaekers, Bram; Armstrong, Nigel; Misso, Kate; Severens, Hans; Kleijnen, Jos

    2014-01-01

    markdownabstract__Abstract__ Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment with standard chemotherapy. Patients with NSCLC are therefore tested for EGFR-TK tumour gene mutations to inform treatment decisions. There are a variety of tests available to detect these mutations. T...

  16. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

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    Ziping WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

  17. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.

    Science.gov (United States)

    Crinò, Lucio; Dansin, Eric; Garrido, Pilar; Griesinger, Frank; Laskin, Janessa; Pavlakis, Nick; Stroiakovski, Daniel; Thatcher, Nick; Tsai, Chun-Ming; Wu, Yi-long; Zhou, Caicun

    2010-08-01

    Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily

  18. Phase I Results of Vinorelbine With Concurrent Radiotherapy in Elderly Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer: West Japan Thoracic Oncology Group (WJTOG3005-DI)

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    Harada, Hideyuki, E-mail: h.harada@scchr.jp [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Seto, Takashi [Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka (Japan); Igawa, Satoshi [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Tsuya, Asuka [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Wada, Mayuko [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Kaira, Kyoichi; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Hayakawa, Kazushige [Department of Radiology, Kitasato University School of Medicine, Kanagawa (Japan); Nishimura, Tetsuo [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan); Masuda, Noriyuki [Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Sunto-gun, Shizuoka (Japan)

    2012-04-01

    Purpose: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m{sup 2} in Level 1 and 25 mg/m{sup 2} in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m{sup 2}) on Days 1 and 8 every 3 weeks for two cycles. Results: Four patients were enrolled at Level 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively. Conclusions: Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.

  19. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS).

    Science.gov (United States)

    Smit, Egbert F; Wu, Yi-Long; Gervais, Radj; Zhou, Caicun; Felip, Enriqueta; Feng, Jifeng; Guclu, Salih Zeki; Hoiczyk, Mathias; Dorokhova, Elena; Freudensprung, Ulrich; Grange, Susan; Perez-Moreno, Pablo Diego; Mitchell, Lada; Reck, Martin

    2016-09-01

    Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150). Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity. progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety. A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR]=1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P=0.671). Median OS was 6.8 months in both arms (unstratified HR=1.03, 95% CI: 0.80-1.32; unstratified log-rank P=0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced ≥1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade ≥3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy. Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528.

    Science.gov (United States)

    Dy, Grace K; Mandrekar, Sumithra J; Nelson, Garth D; Meyers, Jeffrey P; Adjei, Araba A; Ross, Helen J; Ansari, Rafat H; Lyss, Alan P; Stella, Philip J; Schild, Steven E; Molina, Julian R; Adjei, Alex A

    2013-01-01

    The purpose of this study was to assess the safety and efficacy of gemcitabine and carboplatin with (arm A) or without (arm B) daily oral cediranib as first-line therapy for advanced non-small-cell lung cancer. A lead-in phase to determine the tolerability of gemcitabine 1000 mg/m on days 1 and 8, and carboplatin on day 1 at area under curve 5 administered every 21 days with cediranib 45 mg once daily was followed by a 2 (A):1 (B) randomized phase II study. The primary end point was confirmed overall response rate (ORR) with 6-month progression-free survival (PFS6) rate in arm A as secondary end point. Polymorphisms in genes encoding cediranib targets and transport were correlated with treatment outcome. On the basis of the safety assessment, cediranib 30 mg daily was used in the phase II portion. A total of 58 and 29 evaluable patients were accrued to arms A and B. Patients in A experienced more grade 3+ nonhematologic adverse events, 71% versus 45% (p = 0.01). The ORR was 19% (A) versus 20% (B) (p = 1.0). PFS6 in A was 48% (95% confidence interval: 35%-62%), thus meeting the protocol-specified threshold of at least 40%. The median overall survival was 12.0 versus 9.9 months (p = 0.10). FGFR1 rs7012413, FGFR2 rs2912791, and VEGFR3 rs11748431 polymorphisms were significantly associated with decreased overall survival (hazard ratio 2.78-5.01, p = 0.0002-0.0095). The trial did not meet its primary end point of ORR but met its secondary end point of PFS6. The combination with cediranib 30 mg daily resulted in increased toxicity. Pharmacogenetic analysis revealed an association of FGFR and VEGFR variants with survival.

  1. Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

    Science.gov (United States)

    Socinski, M A; Clark, J A; Halle, J; Steagall, A; Kaluzny, B; Rosenman, J G

    1997-08-01

    Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

  2. Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib.

    Science.gov (United States)

    Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen

    2017-09-01

    This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p  = .02; 2.69 [1.60-4.51], p  lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.

  3. A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer. Reducing the interobserver variability in multicentre clinical studies

    International Nuclear Information System (INIS)

    Schimek-Jasch, Tanja; Prokic, Vesna; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula; Troost, Esther G.C.; Ruecker, Gerta; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael

    2015-01-01

    Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study

  4. Development of the Japanese version of an information aid to provide accurate information on prognosis to patients with advanced non-small-cell lung cancer receiving chemotherapy: a pilot study.

    Science.gov (United States)

    Nakano, Kikuo; Kitahara, Yoshihiro; Mito, Mineyo; Seno, Misato; Sunada, Shoji

    2018-02-27

    Without explicit prognostic information, patients may overestimate their life expectancy and make poor choices at the end of life. We sought to design the Japanese version of an information aid (IA) to provide accurate information on prognosis to patients with advanced non-small-cell lung cancer (NSCLC) and to assess the effects of the IA on hope, psychosocial status, and perception of curability. We developed the Japanese version of an IA, which provided information on survival and cure rates as well as numerical survival estimates for patients with metastatic NSCLC receiving first-line chemotherapy. We then assessed the pre- and post-intervention effects of the IA on hope, anxiety, and perception of curability and treatment benefits. A total of 20 (95%) of 21 patients (65% male; median age, 72 years) completed the IA pilot test. Based on the results, scores on the Distress and Impact Thermometer screening tool for adjustment disorders and major depression tended to decrease (from 4.5 to 2.5; P = 0.204), whereas no significant changes were seen in scores for anxiety on the Japanese version of the Support Team Assessment Schedule or in scores on the Hearth Hope Index (from 41.9 to 41.5; p = 0.204). The majority of the patients (16/20, 80%) had high expectations regarding the curative effects of chemotherapy. The Japanese version of the IA appeared to help patients with NSCLC maintain hope, and did not increase their anxiety when they were given explicit prognostic information; however, the IA did not appear to help such patients understand the goal of chemotherapy. Further research is needed to test the findings in a larger sample and measure the outcomes of explicit prognostic information on hope, psychological status, and perception of curability.

  5. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil; Thompson, Lora M.; Yue, Binglin; Stevens, Craig W.; Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee; Kim, Sungjune; Chiappori, Alberto

    2014-01-01

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause

  6. Time-Series Modeling and Simulation for Comparative Cost-Effective Analysis in Cancer Chemotherapy: An Application to Platinum-Based Regimens for Advanced Non-small Cell Lung Cancer.

    Science.gov (United States)

    Chisaki, Yugo; Nakamura, Nobuhiko; Yano, Yoshitaka

    2017-01-01

    The purpose of this study was to propose a time-series modeling and simulation (M&S) strategy for probabilistic cost-effective analysis in cancer chemotherapy using a Monte-Carlo method based on data available from the literature. The simulation included the cost for chemotherapy, for pharmaceutical care for adverse events (AEs) and other medical costs. As an application example, we describe the analysis for the comparison of four regimens, cisplatin plus irinotecan, carboplatin plus paclitaxel, cisplatin plus gemcitabine (GP), and cisplatin plus vinorelbine, for advanced non-small cell lung cancer. The factors, drug efficacy explained by overall survival or time to treatment failure, frequency and severity of AEs, utility value of AEs to determine QOL, the drugs' and other medical costs in Japan, were included in the model. The simulation was performed and quality adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) were calculated. An index, percentage of superiority (%SUP) which is the rate of the increased cost vs. QALY-gained plots within the area of positive QALY-gained and also below some threshold values of the ICER, was calculated as functions of threshold values of the ICER. An M&S process was developed, and for the simulation example, the GP regimen was the most cost-effective, in case of threshold values of the ICER=$70000/year, the %SUP for the GP are more than 50%. We developed an M&S process for probabilistic cost-effective analysis, this method would be useful for decision-making in choosing a cancer chemotherapy regimen in terms of pharmacoeconomic.

  7. Regional Lymph Node Uptake of [{sup 18}F]Fluorodeoxyglucose After Definitive Chemoradiation Therapy Predicts Local-Regional Failure of Locally Advanced Non-Small Cell Lung Cancer: Results of ACRIN 6668/RTOG 0235

    Energy Technology Data Exchange (ETDEWEB)

    Markovina, Stephanie [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States); Duan, Fenghai [Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island (United States); Snyder, Bradley S. [Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island (United States); Siegel, Barry A. [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States); Machtay, Mitchell [Department of Radiation Oncology, Case Western Reserve University, Cleveland, Ohio (United States); Bradley, Jeffrey D., E-mail: jbradley@radonc.wustl.edu [Mallinckrodt Institute of Radiology and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri (United States)

    2015-11-01

    Purpose: The American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [{sup 18}F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes. Methods and Materials: Included for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling. Results: Of 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001). Conclusions: High residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local

  8. A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

    Science.gov (United States)

    Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

    2015-06-01

    Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study

  9. Magnitude of the benefit of progression-free survival as a potential surrogate marker in phase 3 trials assessing targeted agents in molecularly selected patients with advanced non-small cell lung cancer: systematic review.

    Directory of Open Access Journals (Sweden)

    Katsuyuki Hotta

    Full Text Available BACKGROUND: In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC, overall survival (OS as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. METHODS AND FINDINGS: We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design. Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs (0.99 vs. 1.04, the former exhibited greater progression-free survival-hazard ratios (PFS-HR (mean, 0.40 vs. 1.01; P<0.01. A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%. The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01. An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%. CONCLUSION: The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial.

  10. Phase II study of tailored S-1 monotherapy with a 1-week interval after a 2-week dosing period in elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Goto, Hisatsugu; Okano, Yoshio; Machida, Hisanori; Hatakeyama, Nobuo; Ogushi, Fumitaka; Haku, Takashi; Kanematsu, Takanori; Urata, Tomoyuki; Kakiuchi, Soji; Hanibuchi, Masaki; Sone, Saburo; Nishioka, Yasuhiko

    2018-01-01

    S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established. We conducted a phase II trial to evaluate the efficacy and safety of a 2-week S-1 monotherapy treatment followed by a 1-week interval as a first-line treatment of elderly NSCLC patients, by adjusting the dose based on the individual creatinine clearance (Ccr) and body surface area (BSA). The primary endpoint was the disease control rate. Forty patients were enrolled. The disease control and response rates were 89.5% (95% confidence interval [CI] = 79.8-99.2) and 7.9% (95% CI = 0.0-16.4), respectively. The median progression-free survival and overall survival times were 4.4 months (95% CI = 4.2-8.5) and 17.0 months (95% CI = 11.2-18.7), respectively. Neutropenia, anorexia, hyponatremia, hypokalemia, and pneumonia of grade ≥ 3 occurred in 5.0%, 7.5%, 5.0%, 2.5%, and 2.5% of patients, respectively. Among the patient-reported outcomes, most of the individual factors in the patients' quality of life, including upper intestine-related symptoms improved with the treatment, except for dyspnea, which slightly albeit continuously worsened throughout the study. In elderly patients with previously untreated advanced NSCLC, a 2-week S-1 monotherapy treatment, tailored to both the Ccr and BSA, with a 1-week interval was well tolerated and demonstrated promising efficacy. This study was registered at the University Hospital Medical Information Network (UMIN) Center (ID: UMIN000002035), Japan. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  11. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dilling, Thomas J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Extermann, Martine [Department of Senior Adult Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Jongphil [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Thompson, Lora M. [Department of Supportive Care Medicine, Moffitt Cancer Center, Tampa, Florida (United States); Yue, Binglin [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Stevens, Craig W. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Sungjune [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Chiappori, Alberto, E-mail: alberto.chiappori@moffitt.org [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States)

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  12. The early predictive value of a decrease of metabolic tumor volume in repeated 18F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

    International Nuclear Information System (INIS)

    Huang, Wei; Liu, Bo; Fan, Min; Zhou, Tao; Fu, Zheng; Zhang, Zicheng; Li, Hongsheng; Li, Baosheng

    2015-01-01

    Highlights: •The patients underwent the second FDG PET during the early stage of concurrent chemoradiotherapy (CCRT). •To our knowledge, this could be the first study showing that the repeated FDG PET during the early stage of CCRT has added value by being a prognostic factor for recurrence of the locally advanced NSCLC patients. •This is a result of continuous research. •The decrease of MTV was the only significant risk factor for recurrence. -- Abstract: Purpose: The aim of this study is to investigate the value of [ 18 F] fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). Methods: A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan–Meier curves. Results: Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan–Meier curve successfully. Conclusion: The prospective study has reinforced the early predictive value of MTV in repeated 18 F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who underwent CCRT. A

  13. First-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer : analysis of the Italian patients enrolled in the SAiL study.

    Science.gov (United States)

    Bearz, Alessandra; Passalacqua, Rodolfo; Alabiso, Oscar; Cinieri, Saverio; Gridelli, Cesare; Cravesana, Claudia; Crinò, Lucio

    2012-11-01

    First-line bevacizumab-based therapy has been shown to improve outcomes in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The recent international phase IV SAiL study (a Study of Avastin [bevacizumab] in combination with platinum-containing chemotherapy in patients with advanced or recurrent non-squamous cell Lung cancer) evaluated the safety and efficacy of bevacizumab combined with standard chemotherapy regimens in routine clinical practice. Here we report the results of a subanalysis of baseline characteristics and efficacy data for Italian patients enrolled in SAiL. In the SAiL study, patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC received bevacizumab (7.5 or 15 mg/kg) every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Efficacy was assessed in terms of time to disease progression (TTP) and overall survival (OS). The Italian intent-to-treat population comprised 215 patients from a SAiL population of 2212 patients. At baseline, Italian patients tended to have less advanced disease than the overall population. Thus, the proportion of patients at enrollment with tumour stage IIIb and IV was 23.7 and 76.3 %, respectively, for the Italian population versus 19.7 and 80.3 % for the whole SAiL population. In addition, a higher proportion of Italian patients had an Eastern Cooperative Oncology Group performance status of 0 (72.6 vs. 37.2 %) and the prevalence of co-morbid conditions was lower in Italian patients (59.5 % of Italian patients reported a co-morbid condition and 60.0 % were receiving non-oncological treatment compared with 73.3 and 73.4 %, respectively, of SAiL patients overall). The mean exposures to bevacizumab and to chemotherapy were comparable between the Italian patient group and overall patient population, although cisplatin doublets were more commonly employed in Italian patients whereas carboplatin doublets were more

  14. Randomized phase II chemotherapy and radiotherapy trial for patients with locally advanced inoperable non-small-cell lung cancer: long-term follow-up of RTOG 92-04

    International Nuclear Information System (INIS)

    Komaki, R.; Seiferheld, W.; Ettinger, D.; Lee, J.S.; Movsas, B.; Sause, W.

    2002-01-01

    Purpose: The standard treatment for patients with locally advanced inoperable non-small-cell lung cancer and good prognostic factors has become combined chemotherapy (ChT) and radiotherapy (RT). However, the sequencing of the two modalities, as well as fractionation of RT, has been controversial. The Radiation Therapy Oncology Group (RTOG) Study 92-04 was a randomized Phase II study designed to evaluate further the toxicity and efficacy of 2 different strategies of chemoradiation evaluated in 2 prior RTOG Phase II studies. Methods: Patients with Stage II or III medically inoperable or unresectable non-small-cell lung cancer, good performance status, and minimal weight loss were enrolled into a prospective randomized Phase II RTOG study. Arm 1 consisted of induction ChT (vinblastine 5 mg/m 2 i.v. bolus weekly for the first 5 weeks, and cisplatin, 100 mg/m 2 i.v. on Days 1 and 29) followed by concurrent ChT/RT (cisplatin 75 mg/m 2 i.v. on Days 50, 71, and 92) during thoracic radiotherapy (63 Gy in 34 fractions during 7 weeks starting on Day 50). Arm 2 was concurrent ChT and hyperfractionated RT starting on Day 1 with a total dose of 69.6 Gy in 58 fractions during 6 weeks, 1.2 Gy/fraction b.i.d. ChT consisted of cisplatin, 50 mg/m 2 i.v. on Days 1 and 8, and oral VP-16, 50 mg b.i.d. for 10 days only on the days of thoracic radiotherapy repeated on Day 29. Results: A total of 168 patients were entered between 1992 and 1994, and 163 patients were eligible for analysis. Eighty-one patients were treated in Arm 1 and 82 patients in Arm 2. Pretreatment characteristics, including age, gender, Karnofsky performance status, histologic features, and stage, were similar. The incidence of acute esophagitis was significantly higher among patients treated in Arm 2 than among those treated in Arm 1 (p<0.0001). The incidence of acute hematologic toxicity was significantly higher among patients treated in Arm 1 (p=0.01 for anemia and p=0.03 for other hematologic toxicities) than among

  15. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Chen JH

    2016-04-01

    Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

  16. Non-small cell lung cancer in never smokers: a clinical entity to be identified.

    Science.gov (United States)

    Santoro, Ilka Lopes; Ramos, Roberta Pulcheri; Franceschini, Juliana; Jamnik, Sergio; Fernandes, Ana Luisa Godoy

    2011-01-01

    It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among never-smokers with non-small cell lung cancer. All consecutive non-small cell lung cancer patients diagnosed (n = 285) between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current) were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable), gender (female vs. male), smoking status (never- vs. ever-smoker), the Karnofsky Performance Status Scale (continuous variable), histological type (adenocarcinoma vs. non-adenocarcinoma), AJCC staging (early vs. advanced staging), and treatment (chemotherapy and/or radiotherapy vs. the best treatment support). Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32%) and have adenocarcinoma (70% vs. 51%). Overall median survival was 15.7 months (95% CI: 13.2 to 18.2). The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

  17. Non-small cell lung cancer in never smokers: a clinical entity to be identified

    Directory of Open Access Journals (Sweden)

    Ilka Lopes Santoro

    2011-01-01

    Full Text Available OBJECTIVES: It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among neversmokers with non-small cell lung cancer. METHODS: All consecutive non-small cell lung cancer patients diagnosed (n = 285 between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable, gender (female vs. male, smoking status (never- vs. ever-smoker, the Karnofsky Performance Status Scale (continuous variable, histological type (adenocarcinoma vs. non-adenocarcinoma, AJCC staging (early vs. advanced staging, and treatment (chemotherapy and/or radiotherapy vs. the best treatment support. RESULTS: Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32% and have adenocarcinoma (70% vs. 51%. Overall median survival was 15.7 months (95% CI: 13.2 to 18.2. The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. CONCLUSIONS: Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

  18. Astragalus-containing Traditional Chinese Medicine, with and without prescription based on syndrome differentiation, combined with chemotherapy for advanced non-small-cell lung cancer: a systemic review and meta-analysis.

    Science.gov (United States)

    Wang, S F; Wang, Q; Jiao, L J; Huang, Y L; Garfield, D; Zhang, J; Xu, L

    2016-06-01

    Traditional Chinese Medicine (tcm) is used in China as part of the treatment for non-small-cell lung cancer (nsclc) and often includes prescription of herbal therapy based on syndrome differentiation. Studies of various Astragalus-based Chinese medicines combined with platinum-based chemotherapy in the treatment of lung cancer are popular in East Asia, particularly in China. The aim of the present study was to perform a systematic review and meta-analysis comparing platinum-based chemotherapy alone with platinum-based chemotherapy plus Astragalus-based Chinese botanicals, with and without prescription based on syndrome differentiation, as first-line treatment for advanced nsclc. We searched the Chinese Biomedical Literature database, the China National Knowledge Internet, the VIP Chinese Science and Technology Periodicals Database, PubMed, embase, the Cochrane databases, and abstracts presented at meetings of the American Society of Clinical Oncology, the World Conference on Lung Cancer, the European Society for Medical Oncology, and the Chinese Society of Clinical Oncology for all eligible studies. Endpoints were overall survival; 1-year, 2-year, and 3-year survival rates; performance status; overall response rate; and grade 3 or 4 adverse events. Subgroup analyses based on herbal formulae individualized using syndrome differentiation or on oral or injection patent medicines were performed using the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.) and a fixed-effects or random-effects model in case of heterogeneity. Results are expressed as a hazard ratio (hr) or relative risk (rr), with corresponding 95% confidence intervals (cis). Seventeen randomized studies with scores on the Jadad quality scale of 2 or more, representing 1552 patients, met the inclusion criteria. Compared with platinum-based chemotherapy alone, the addition of Astragalus-based tcm to chemotherapy was associated with significantly increased overall survival

  19. Optimal FDG PET/CT volumetric parameters for risk stratification in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial

    Energy Technology Data Exchange (ETDEWEB)

    Salavati, Ali [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); University of Minnesota, Department of Radiology, Minneapolis, MN (United States); Duan, Fenghai [Brown University School of Public Health, Department of Biostatistics and Center for Statistical Sciences, Providence, RI (United States); Snyder, Bradley S. [Brown University School of Public Health, Center for Statistical Sciences, Providence, RI (United States); Wei, Bo [Emory University, Department of Biostatistics, Rollins School of Public Health, Atlanta, GA (United States); Houshmand, Sina; Alavi, Abass [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Khiewvan, Benjapa [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Mahidol University, Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Bangkok (Thailand); Opanowski, Adam [ACR Center for Research and Innovation, American College of Radiology, Philadelphia, PA (United States); Simone, Charles B. [University of Maryland Medical Center, Department of Radiation Oncology, Baltimore, MD (United States); Siegel, Barry A. [Washington University School of Medicine, Mallinckrodt Institute of Radiology and the Alvin J. Siteman Cancer Center, St, Louis, MO (United States); Machtay, Mitchell [Case Western Reserve University and University Hospitals Case Medical Center, Department of Radiation Oncology, Cleveland, OH (United States)

    2017-11-15

    In recent years, multiple studies have demonstrated the value of volumetric FDG-PET/CT parameters as independent prognostic factors in patients with non-small cell lung cancer (NSCLC). We aimed to determine the optimal cut-off points of pretreatment volumetric FDG-PET/CT parameters in predicting overall survival (OS) in patients with locally advanced NSCLC and to recommend imaging biomarkers appropriate for routine clinical applications. Patients with inoperable stage IIB/III NSCLC enrolled in ACRIN 6668/RTOG 0235 were included. Pretreatment FDG-PET scans were quantified using semiautomatic adaptive contrast-oriented thresholding and local-background partial-volume-effect-correction algorithms. For each patient, the following indices were measured: metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, SUVmean, partial-volume-corrected TLG (pvcTLG), and pvcSUVmean for the whole-body, primary tumor, and regional lymph nodes. The association between each index and patient outcome was assessed using Cox proportional hazards regression. Optimal cut-off points were estimated using recursive binary partitioning in a conditional inference framework and used in Kaplan-Meier curves with log-rank testing. The discriminatory ability of each index was examined using time-dependent receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC(t)). The study included 196 patients. Pretreatment whole-body and primary tumor MTV, TLG, and pvcTLG were independently prognostic of OS. Optimal cut-off points were 175.0, 270.9, and 35.5 cm{sup 3} for whole-body TLG, pvcTLG, and MTV, and were 168.2, 239.8, and 17.4 cm{sup 3} for primary tumor TLG, pvcTLG, and MTV, respectively. In time-dependent ROC analysis, AUC(t) for MTV and TLG were uniformly higher than that of SUV measures over all time points. Primary tumor and whole-body parameters demonstrated similar patterns of separation for those patients above versus below the optimal cut

  20. Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain

    Directory of Open Access Journals (Sweden)

    Lister J

    2012-10-01

    Full Text Available Johanna Lister,1 Sanja Stanisic,1 Klaus Kaier,2 Christian Hagist,2 Dmitry Gultyaev,1 Stefan Walzer31Analytica LA-SER International Inc, Lörrach, Germany; 2Research Centre for Generational Contracts, University of Freiburg, Freiburg, Germany; 3F Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, SwitzerlandBackground: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain.Methods: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses.Results: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working full-time and the proportion of patients who were able to return to work.Conclusion: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.Keywords: non-small-cell lung cancer, bevacizumab, chemotherapy, economic model, France, Germany, Italy, Spain

  1. Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.

    Science.gov (United States)

    Esteban, E; Majem, M; Martinez Aguillo, M; Martinez Banaclocha, N; Dómine, M; Gómez Aldaravi, L; Juan, O; Cajal, R; Gonzalez Arenas, M C; Provencio, M

    2015-06-01

    The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients. All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations. From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%). The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in

  2. Current and future molecular diagnostics in non-small-cell lung cancer.

    Science.gov (United States)

    Li, Chun Man; Chu, Wing Ying; Wong, Di Lun; Tsang, Hin Fung; Tsui, Nancy Bo Yin; Chan, Charles Ming Lok; Xue, Vivian Wei Wen; Siu, Parco Ming Fai; Yung, Benjamin Yat Ming; Chan, Lawrence Wing Chi; Wong, Sze Chuen Cesar

    2015-01-01

    The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.

  3. Epidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: An Evidence-Based Analysis.

    Science.gov (United States)

    2010-01-01

    In February 2010, the Medical Advisory Secretariat (MAS) began work on evidence-based reviews of the literature surrounding three pharmacogenomic tests. This project came about when Cancer Care Ontario (CCO) asked MAS to provide evidence-based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario.Evidence-based analyses have been prepared for each of these technologies. These have been completed in conjunction with internal and external stakeholders, including a Provincial Expert Panel on Pharmacogenetics (PEPP). Within the PEPP, subgroup committees were developed for each disease area. For each technology, an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative (THETA) and is summarized within the reports.THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE MAS WEBSITE AT: http://www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER: An Evidence-Based AnalysisEpidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: an Evidence-Based AnalysisK-RAS testing in Treatment Decisions for Advanced Colorectal Cancer: an Evidence-Based Analysis The Medical Advisory Secretariat undertook a systematic review of the evidence on the clinical effectiveness and cost-effectiveness of epidermal growth factor receptor (EGFR) mutation testing compared with no EGFR mutation testing to predict response to tyrosine kinase inhibitors (TKIs), gefitinib (Iressa(®)) or erlotinib (Tarceva(®)) in patients with advanced non-small cell lung cancer (NSCLC). TARGET POPULATION AND CONDITION With an estimated 7,800 new cases and 7,000 deaths last year, lung cancer is the leading cause of cancer

  4. Effectiveness of palliative radiotherapy in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Chmielewska, E.; Jaskiewicz, P.

    2001-01-01

    Lung cancer is the most frequent malignant neoplasm in Poland. During the last 25 years it has become the first reason of death of men and the second of women in Poland. Patients with non-small cell lung cancer constitute 75% of all lung cancer patients. The therapy of choice for the advanced, non-small cell lung cancer is radiotherapy with palliative assumption. Many papers indicate that this therapy has no influence on long-term survival, hence it is aimed at reducing the symptoms. The therapy brings relief to 70-80% of patients. At present no ot