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Sample records for advanced nonsquamous non-small

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

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    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

  2. Clinical Investigation of Efficacy of Third-line and Beyond Pemetrexed Treatment in Advanced Non-squamous Non-small Cell Lung Cancer

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    Fei YU

    2012-02-01

    Full Text Available Background and objective Pemetrexed in combination with platinum or a single-agent has been approved for the first- and second-line treatment of non-small cell lung cancer (NSCLC. However, the role of pemetrexed therapy in the third-line and beyond treatment of NSCLC has yet to be generally accepted. The present retrospective study reports the efficacy and safety of pemetrexed in the third-line and beyond treatment of advanced non-squamous NSCLC. Methods A total of 46 patients with advanced non-squamous NSCLC received a combination of pemetrexed plus platinum or a single-agent after multi-line treatment failed to yield positive results. Results Of the 46 patients who participated in the study, 7 achieved partial responses, 20 reached a stage of stable disease, and 19 reached a stage of progressive disease. The over-all object response rate was 15.2% and the disease control rate (DCR was 58.7%. The median progression-free survival time was 3.0 months. Pemetrexed in combination with platinum yielded a higher DCR than the pemetrexed plus single-agent treatment (P=0.043. Common adverse events included nausea, vomiting and myelosuppression. Conclusion Administration of pemetrexed after failure of multi-line treatment is clinically beneficial to patients with advanced non-squamous NSCLC. The toxic effects of the treatment appear to be tolerable.

  3. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

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    Xiao HQ

    2016-03-01

    Full Text Available Huai-Qing Xiao,1 Rong-Hua Tian,2 Zhi-Hao Zhang,1 Kai-Qi Du,1 Yi-Ming Ni3 1Department of Cardiothoracic Surgery, Zhejiang Corps Hospital, Chinese People’s Armed Police Force, Jiaxing, Zhejiang Province, People’s Republic of China; 2Department of Respiratory, Affiliated Haian People’s Hospital of Nantong University, Haian, Jiangsu, People’s Republic of China; 3Department of Cardiothoracic Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Purpose: To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC through a trial-level meta-analysis. Methods: Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library. All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR, progression-free survival (PFS, and overall survival (OS were extracted and analyzed using comprehensive meta-analysis software (version 2.0. Results: A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%, with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01 but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084 in advanced nonsquamous NSCLC patients. Conclusion: Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our

  4. Comparison of liposomal cisplatin versus cisplatin in non-squamous cell non-small-cell lung cancer

    OpenAIRE

    Stathopoulos, G. P.; Antoniou, D.; Dimitroulis, J.; STATHOPOULOS, J.; Marosis, K.; Michalopoulou, P.

    2011-01-01

    Purpose Liposomal cisplatin was developed to reduce the systemic toxicity of cisplatin, particularly the nephrotoxicity, and it has been used in combination with other agents in pancreatic and head and neck cancers and non-small-cell lung cancer (NSCLC). Our objective was to compare the effectiveness of lipoplatin combined with paclitaxel versus cisplatin with paclitaxel in advanced non-squamous NSCLC. Methods During 2007–2010, 202 patients with non-squamous NSCLC (stage IIIB and IV) were rec...

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

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    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.

  6. Doublet chemotherapy with cisplatin and pemetrexed is associated with a favorable outcome in patients with advanced non-squamous non-small-cell lung cancer who are eligible for bevacizumab and maintenance therapy.

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    Nakashima, Kazuhisa; Murakami, Haruyasu; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Endo, Masahiro; Takahashi, Toshiaki

    2016-11-01

    The previous AVAPERL trial demonstrated that induction therapy with first-line cisplatin (CDDP), pemetrexed (PEM) and bevacizumab (BEV), followed by continuation maintenance therapy with PEM+BEV, improved the progression-free survival (PFS) and overall survival (OS) compared with BEV alone (median PFS, 10.2 vs. 6.6 months and median OS, 19.8 vs. 15.9 months, respectively) in patients with advanced non-squamous non-small-cell lung cancer (non-Sq NSCLC). However, those findings were based on selected patients who were eligible for BEV and maintenance therapy. To assess the efficacy of CDDP+PEM as first-line therapy in selected patients depending on their eligibility for BEV and maintenance therapy, consecutive patients with non-Sq NSCLC who received first-line chemotherapy with CDDP+PEM at the Shizuoka Cancer Center (Shizuoka, Japan) between July, 2009 and December, 2013 were retrospectively reviewed. A total of 160 patients were assessed, including 92 who were eligible and 68 who were not eligible for BEV treatment. In the BEV-eligible group, CDDP+PEM treatment followed by maintenance PEM exhibited significantly superior efficacy compared with that in the BEV-ineligible group (median PFS, 5.8 vs. 4.8 months, respectively, P=0.013; and median OS, 21.3 vs. 12.6 months, respectively, P=0.0025). In the BEV-eligible group, 60 patients were suitable for maintenance therapy with PEM (group A) and 32 patients were unsuitable (group B). In the BEV-ineligible group, 31 patients were suitable for maintenance therapy with PEM (group C) and 37 patients were unsuitable (group D). In group A, the median PFS and OS were 6.9 and 31.8 months, respectively, compared with 2.4 and 10.5 months in group B, 6.1 and 18.5 months in group C, and 2.8 and 7.7 months in group D. The PFS and OS in group A were significantly better compared with those in the other groups. Thus, the PFS and OS with CDDP+PEM were favorable among patients with advanced non-Sq NSCLC who were eligible for BEV and

  7. Safety and Efficacy of First-Line Bevacizumab Plus Chemotherapy in Elderly Patients with Advanced or Recurrent Nonsquamous Non-small Cell Lung Cancer Safety of Avastin in Lung trial (MO19390)

    NARCIS (Netherlands)

    Laskin, Janessa; Crino, Lucio; Felip, Enriqueta; Franke, Fabio; Gorbunova, Vera; Groen, Harry; Jiang, Guo-liang; Reck, Martin; Schneider, Claus-Peter

    2012-01-01

    Introduction: Safety of Avastin in Lung (MO19390) was an international, open-label, single-arm study, which assessed the safety and efficacy of first-line bevacizumab (Avastin (R)) in combination with standard chemotherapy in patients (n = 2212) with advanced or recurrent non-small cell lung cancer

  8. Association between gene expression profiles and clinical outcome of pemetrexed-based treatment in patients with advanced non-squamous non-small cell lung cancer: exploratory results from a phase II study.

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    Dean A Fennell

    Full Text Available INTRODUCTION: We report exploratory gene-expression profiling data from a single-arm Phase-II-study in patients with non-squamous (nsNSCLC treated with pemetrexed and cisplatin. Previously disclosed results indicated a significant association of low thymidylate-synthase (TS-expression with longer progression-free and overall survival (PFS/OS. METHODS: Treatment-naïve nsNSCLC patients (IIIB/IV received 4 cycles of pemetrexed/cisplatin; non-progressing patients continued on pemetrexed-maintenance. Diagnostic tissue-samples were used to assess TS-expression by immunohistochemistry (IHC and mRNA-expression array-profiling (1,030 lung cancer-specific genes. Cox proportional-hazard models were applied to explore the association between each gene and PFS/OS. Genes significantly correlated with PFS/OS were further correlated with TS-protein expression (Spearman-rank. Unsupervised clustering was applied to all evaluable samples (n = 51 for all 1,030 genes and an overlapping 870-gene subset associated with adenocarcinoma (ADC, n = 47. RESULTS: 51/70 tissue-samples (72.9% were evaluable; 9 of 1,030 genes were significantly associated with PFS/OS (unadjusted p < 0.01, genes: Chromosome 16 open reading frame 89, napsin A, surfactant protein B, aquaporin 4, TRAF2- and Nck-interacting kinase, Lysophosphatidylcholine acyltransferase 1, Interleukin 1 receptor type II, NK2 homeobox 1, ABO glycosyl-transferase; expression for all except IL1R2 correlated negatively with nuclear TS-expression (statistically significant for 5/8 genes, unadjusted p<0.01. Cluster-analysis based on 1,030 genes revealed no clear trend regarding PFS/OS; the ADC-based cluster analysis identified 3 groups (n = 21/11/15 with median (95%CI PFS of 8.1(6.9,NE/2.4(1.2,NE/4.4(1.2,NE months and OS of 20.3(17.5,NE/4.3(1.4,NE/8.3(3.9,NE months, respectively. CONCLUSIONS: These exploratory gene-expression profiling results describe genes potentially linked to low TS-expression. Nine genes were

  9. 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

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    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

  10. Bevacizumab for the treatment of nonsquamous non-small-cell lung cancer in Portugal: a retrospective, multicenter study

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    Estevinho F

    2012-03-01

    Full Text Available Fernanda Estevinho1, Marta Soares2, Isabel Azevedo2, Henrique Queiroga3, Bárbara Parente4, Ulisses Brito5, Encarnação Teixeira6, Renato Sotto-Mayor7, António Araújo81Medical Oncology Resident, Department of Medical Oncology, Portuguese Institute of Oncology, Oporto Center, Oporto, Portugal; 2Medical Oncology Assistant, Department of Medical Oncology, Portuguese Institute of Oncology, Oporto Center, Oporto, Portugal; 3Coordinator of the Oncological Pneumology Consultation, Pneumology Departament of Hospital S João, Oporto, Portugal; 4Director of Pneumology Department, Pneumology Department, Vila Nova de Gaia-Espinho Medical Center, Vila Nova de Gaia, Portugal; 5Director of Pneumology Department, Pneumology Department, Faro Hospital, Faro, Portugal; 6Pneumology assistant, Pneumology Department I, Hospital Santa Maria – Lisbon North Hospital Center, Lisbon, Portugal; 7Head of Service of Pneumology, Pneumology Department I, Hospital Santa Maria – Lisbon North Hospital Center, Lisbon, Portugal; 8Coordinator of Lung Pathology Clinic, Department of Medical Oncology, Portuguese Institute of Oncology, Oporto Center, Oporto, PortugalIntroduction: Lung cancer is the leading cause of cancer-related mortality. In patients with nonsquamous non-small-cell lung cancer (NSCLC stage IIIB/IV treatment with chemotherapy plus bevacizumab led to significant improvements in progression-free and median overall survival (OS.Aim: To report the experience of five Portuguese centers in treating patients with nonsquamous NSCLC in stage IIIB or IV with bevacizumab and chemotherapy regarding survival and toxicity outcomes.Materials and methods: This was a retrospective, multicenter study on patients with nonsquamous stage IIIB/IV NSCLC treated with bevacizumab and chemotherapy from November 2007 to August 2010 through special use permits. We reviewed the medical records, registry of demographic characteristics, treatments provided, treatment responses, adverse

  11. Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer

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    Jaime Jesús

    2010-03-01

    Full Text Available Abstract Background To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC, additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS and overall survival (OS after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. Methods/Design Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2 and cisplatin (75 mg/m2 on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle plus best supportive care (BSC or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from

  12. Design paper: A phase II study of Bevacizumab and Erlotinib in patients with non-Squamous non-small cell lung cancer that is refractory or relapsed after 1-2 previous Treatment (BEST

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    Kim Young H

    2011-05-01

    Full Text Available Abstract Background Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC. We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy. Methods Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned. Discussion We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials. Trial registration This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm.

  13. Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population

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    Arellano Jorge

    2010-01-01

    Full Text Available Abstract Background The objective of this study was to conduct a cost-effectiveness evaluation of pemetrexed compared to docetaxel in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC for patients with predominantly non-squamous histology in the Spanish healthcare setting. Methods A Markov model was designed consisting of stable, responsive, progressive disease and death states. Patients could also experience adverse events as long as they received chemotherapy. Clinical inputs were based on an analysis of a phase III clinical trial that identified a statistically significant improvement in overall survival for non-squamous patients treated with pemetrexed compared with docetaxel. Costs were collected from the Spanish healthcare perspective. Results Outcomes of the model included total costs, total quality-adjusted life years (QALYs, total life years gained (LYG and total progression-free survival (PFS. Mean survival was 1.03 years for the pemetrexed arm and 0.89 years in the docetaxel arm; QALYs were 0.52 compared to 0.42. Per-patient lifetime costs were € 34677 and € 32343, respectively. Incremental cost-effectiveness ratios were € 23967 per QALY gained and € 17225 per LYG. Conclusions Pemetrexed as a second-line treatment option for patients with a predominantly non-squamous histology in NSCLC is a cost-effective alternative to docetaxel according to the € 30000/QALY threshold commonly accepted in Spain.

  14. 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

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    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.......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....

  15. 培美曲塞二线治疗老年非鳞非小细胞肺癌的回顾分析%Efficacy and safety of pemetrexed as the second-line therapy in elderly patients with advanced non-squamous non-small cell lung cancer

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    王若天; 姚舒洋; 张毅; 支修益

    2013-01-01

    Objective: To investigate the efficacy and safety of pemetrexed as the second-line therapy in patients older than 70 years with advanced non-squamous non-smal cel lung cancer . Methods: In a single-centre , pemetrexed as the second-line therapy trial , a total of 58 patients older than 70 years with advanced non-squamous non-smal cel lung cancer,failed in their first-line treatment because of progressive disease or severe adverse events, were assigned to receive pemetrexed 500mg/m2 every 3 week, iv, for 6 cycles. Results:Complete remission (CR) occurred in 0 patients, partial remissions (PR) in 6 patients, stable diseases (SD) in 20 patients, SD lasting more than 6 months in 12 patients and progressive diseases (PD) in 32 patients. total response rate (RR) occurred in 10.3%of patients, and clinical benefit (CR+PR+SD>6 months) 31.0%. The median progression free survival (PFS) was 3.4 (2-8.9) months. Ten patients completed 6-cycle treatment. Predominant toxicity were neutropenia , nausea and fatigue. Conclusion: Pemetrexed as second-line therapy appears to be an efficient and wel-tolerated regimen in patients older than 70 years with advanced non-squamous non-smal cel lung cancer .%目的:观察培美曲塞二线治疗老年非鳞非小细胞肺癌(NSCLC)的疗效和不良反应。方法:收集我院从2012年7月至2013年4月住院治疗的70岁以上的晚期非鳞NSCLC患者58例并进行疗效和不良反应回顾性分析。患者均为一线化疗失败或不能耐受者。采用培美曲塞500mg ·m-2静脉滴注,每3周1次,共6个周期。结果:本组完全缓解(CR)0例,部分缓解(PR)6例,疾病稳定(SD)20例,SD持续时间大于6个月的12例,疾病进展(PD)32例。总有效率(RR=CR+PR)为10.3%,临床获益率(CR+PR+SD>6个月)为31.0%,中位无疾病进展时间(PFS)为3.4个月(2.0~8.9个月)。完成6周期治疗的患者10例。主要毒性反应为骨髓抑制、胃

  16. Chemotherapy in non-small cell lung cancer:opportunities for advancement

    Institute of Scientific and Technical Information of China (English)

    Mani Akhtari; Eric H Bernicker; Bin S Teh

    2016-01-01

    Locally advanced non-small cell lung cancer (NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is significant interest in finding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical Oncology entitled“PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer”, compared two different chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received con-solidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no difference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not offer a clinical advantage over standard cisplatin plus etopo-side. There are some subpopulations who might still benefit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.

  17. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

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    Pranshu eBansal

    2016-05-01

    Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

  18. Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer.

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    Dang, Thu Oanh; Ogunniyi, Adebayo; Barbee, Meagan S; Drilon, Alexander

    2016-01-01

    The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

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

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    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.

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

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    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.

  1. Pemetrexed/Carboplatin/Bevacizumab followed by Maintenance Pemetrexed/Bevacizumab in Hispanic Patients with Non-Squamous Non-Small Cell Lung Cancer: Outcomes according to Thymidylate Synthase Expression

    Science.gov (United States)

    Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Cuello, Mauricio; Corrales, Luis; Martín, Claudio; Ortiz, Carlos; Franco, Sandra; Rosell, Rafael

    2016-01-01

    Objective To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity. Results One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1–32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9–10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2–32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6–12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response. Conclusion Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and

  2. Afatinib treatment in advanced non-small cell lung cancer

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    Hurwitz JL

    2011-10-01

    Full Text Available Jane L Hurwitz, Paula Scullin, Lynn CampbellDepartment of Medical Oncology, Northern Ireland Cancer Centre, Belfast, UKAbstract: Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC, prognosis for these patients remains poor. Small molecule epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have however provided a new therapeutic option in this disease setting and EGFR mutation testing is now routine practice for newly diagnosed NSCLC patients. A proportion of patients will not respond to first-generation EGFR-TKIs however, and those who do will ultimately develop resistance and disease relapse. Next-generation EGFR-TKIs which inhibit multiple members of the EGFR family are being developed in order to increase sensitivity and overcome resistance to existing agents. Afatinib (BIBW 2992 is an oral, irreversible inhibitor of EGFR and HER2 tyrosine kinases and is the most advanced of these agents in clinical development. Pre-clinical and early-phase clinical trials have demonstrated a favorable safety profile as a single agent and in combination with other anti-cancer agents, and provide evidence of clinical activity in advanced NSCLC. The LUX-Lung trials suggest that for selected patients, afatinib offers symptomatic improvement and prolonged progression-free survival, although this has not yet translated into improved overall survival. This article aims to review the use of EGFR-TKIs in the management of advanced NSCLC and the mechanisms underlying resistance to these agents. We will discuss the current pre-clinical and clinical data regarding afatinib, its potential to overcome resistance to first-generation TKIs, and its emerging role in advanced NSCLC treatment.Keywords: EGFR, tyrosine kinase inhibitor, mutation, LUX-lung

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

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    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.

  4. Advances in Immunotherapies for Non-small Cell Lung Cancer

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    Yuan HE

    2014-03-01

    Full Text Available Globally, Lung cancer is the leading cause of cancer-related death of high morbidity and mortality with poor prognosis, which needs some more effective and less toxic therapies. The immunotherapies offer a novel approach for the treatment of patients with non-small cell lung cancer (NSCLC in both the adjuvant and palliative disease settings. A number of promising immunotherapies based on different mechanism have now been evaluated showing an increasing response rate. Moreover, further phase II/III clinical trials will be indicated to explore its value. These include checkpoint inhibitors (anti-CTLA4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody, active vaccination (L-BLP25 liposome vaccine, Belagenpumatucel-L vaccine, MAGE-A3 protein vaccine and adoptive vaccination (CIK cells. The purpose of this paper will draw a summary on the theory, clinical trials, toxicity and problems to be solved of the immunotherapies in NSCLC.

  5. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Science.gov (United States)

    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.

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

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    Minami Seigo

    2012-07-01

    Full Text Available Abstract Background 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. Methods 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/m2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2 orally on days 2–16. Results 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. Conclusions Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC.

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

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    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

  8. Challenges in optimizing chemoradiation in locally advanced non small-cell lung cancers in India

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    Sushma Agrawal

    2013-01-01

    Full Text Available Data supporting use of concurrent chemoradiation in locally advanced lung cancers comes from clinical trials from developed countries. Applicability and outcomes of such schedules in developing countries is not widely reported. There are various challenges in delivering chemoradiation in locally advanced non small cell lung cancer in developing countries which is highlighted by an audit of patients treated with chemoradiation in our center. This article deals with the challenges in the context of a developing country. We conclude that sequential chemoradiotherapy is better tolerated than concurrent chemoradiation in Indian patients with locally advanced non-small cell lung cancers. Patients with stage IIIa, normal weight or overweight, and adequate baseline pulmonary function should be offered concurrent chemoradiation.

  9. Efficacy and Toxicity of Pemetrexed or Gemcitabine Combined with Cisplatin in the Treatment of Patients with Advanced Non-small Cell Lung Cancer

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    Xingsheng HU

    2012-10-01

    Full Text Available Background and objective Due to the various inter-individual differences in the biological characteristics of tumor cells, as well as issues on the efficacy, adverse reactions, and defects of existing drugs, we compared the clinical efficacy and toxicity of pemetrexed and gemcitabine combined with cisplatin for the treatment of previously untreated advanced non-small cell lung cancer (NSCLC. Methods 251 patients were randomly divided into pemetrexed combined with cisplatin group (PP group with 127 cases and gemcitabine combined with cisplatin group (GP group with 124 cases. PP group received pemetrexed 500 mg/m2 iv infusion d1 and cisplatin 75 mg/m2 iv infusion d1, whereas GP group received gemcitabine 1,000 mg/m2 iv infusion d1,8 and cisplatin 75 mg/m2 iv infusion d1. The treatment cycle was once every three weeks. In addition, folic acid, vitamin B12, and dexamethasone were administered in both groups. Results The total clinical effective rates in PP group and GP group were 25.20% and 17.74%, respectively. The total efficiencies of non-squamous cell carcinoma were 27.62% and 16.00%. The tumor progression duration in these two groups was 6.5 and 5.6 months, respectively. The median survival time in the two groups was 16.9 and 17.0 months, respectively, with 59.62% and 65.87% survival rates of 1 year and 27.28% and 27.93% survival rates of 2 years, respectively. The total efficacy of non-squamous cell carcinoma in the PP group was significantly higher than that in GP group. The results were statistically significant. However, there were no significant differences in total response rates, tumor progression duration, and median survival rates of 1 and 2 years. The rate of adverse reactions, including white blood cell reduction, lower platelet count, lower hemoglobin, and hair loss in the PP group was significantly lower than that in the GP group. The results were statistically significant. Conclusion The clinical efficacy of pemetrexed and

  10. Medical treatment of advanced non-small cell lung cancer: progress in 2014

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    Yong SONG

    2015-04-01

    Full Text Available Non-small cell lung cancer is the most common pathological type of lung cancer. Along with the rising incidence in recent years, lung cancer has been the leading cause of death due to malignancies both in our country and worldwide. Due to simplistic therapeutic approach for lung cancer decades ago, those patients suffering from advanced lung cancer had short lifetime, and it was difficult to ensure their life quality. In recent years, many molecular targeted drugs, such as Gefitinib, Erlotinib and Crizotinib etc., have been successively applied in clinical use, and they bring about a substantial prolongation of survival life and improvement in life quality of those patients with advanced lung cancer. In 2014, there was a number of important reports concerning the diagnosis and treatment of non-small cell lung cancer in the annual meetings of either American Society of Clinical Oncology or European Society for Medical Oncology. On the basis of the relevant reports delivered in the conferences, it is our attempt to summarize the recent advances in regard to chemotherapy, molecular targeted therapy, measures to treat TKI therapy resistant cases, and immune therapy, followed by a comment regarding recent advances in the treatment of non-small cell lung cancer in 2014. DOI: 10.11855/j.issn.0577-7402.2015.01.03

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

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    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.

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

    Institute of Scientific and Technical Information of China (English)

    Shu-Hui Yao

    2016-01-01

    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:Progression-free 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.

  13. From Uniplex to Multiplex Molecular Profiling in Advanced Non-Small Cell Lung Carcinoma.

    Science.gov (United States)

    Ileana, Ecaterina E; Wistuba, Ignacio I; Izzo, Julie G

    2015-01-01

    Non-small cell lung carcinoma is a leading cause of cancer death worldwide. Understanding the molecular biology of survival and proliferation of cancer cells led to a new molecular classification of lung cancer and the development of targeted therapies with promising results. With the advances of image-guided biopsy techniques, tumor samples are becoming smaller, and the molecular testing techniques have to overcome the challenge of integrating the characterization of a panel of abnormalities including gene mutations, copy-number changes, and fusions in a reduced number of assays using only a small amount of genetic material. This article reviews the current knowledge about the most frequent actionable molecular abnormalities in non-small cell lung carcinoma, the new approaches of molecular analysis, and the implications of these findings in the context of clinical practice.

  14. Effects of Combined Chinese Drugs and Chemotherapy in Treating Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    陈衍智; 李占东; 高非; 张莹; 孙红; 李萍萍

    2009-01-01

    Objective:To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer(NSCLC).Methods:Sixty-three patients with stageⅢB andⅣNSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table,with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin(NP) chemotherapy,but to the treatment group the Chinese drugs...

  15. [The quality of life after chemotherapy in advanced non-small cell lung cancer patients].

    Science.gov (United States)

    Słowik-Gabryelska, A; Szczepanik, A; Kalicka, A

    1999-01-01

    The intensity of complains, short survival and great number of patients makes many oncologists to apply chemotherapy in advanced non-small cell lung cancer/NSCLC/. The achieved median duration of life after chemotherapy was 6 to 12 month. From the other hand non small cell lung cancer chemotherapy is a big burden even to healthy persons. It can worsen the quality of life. That was the reason we evaluated the quality of life after chemotherapy in advanced non small cell lung cancer patients. Taking into account, that the evaluation of quality of life, used in most diseases is useless in advanced NSCLC patients, for appreciation the quality of life in these cases the lung cancer symptoms scale/LCSS/was adopted. In 110 non small cell lung cancer patients in stage IIIB and IV, who received combined chemotherapy by Le Chevalier/Vindesine, Cisplatin, Cyclophosphamide, Lomustin/or by Rosell/Mitomycin, Cyclophosphamide, Cisplatin/the quality of life was evaluated. In 20-persons control group all patients received the symptomatic treatment. In observed group of 110 patients, tumor regressions after 4 courses of chemotherapy allowed to resect cancer in 14 cases, to apply radiotherapy in 42 and to continue chemiotherapy in 23 persons. In every person from above mentioned group the quality of life was evaluated on the basis of intensity of cancer symptoms, accordingly to LCSS. The intensity of cancer symptoms was compared before and after treatment. There were compared; the innensity of complains, weakness, appetite, malnutrition, and hematological, neurological, performans state as well as respiratory sufficiency, infections, cardiac disorders and pain. Apart it, the side effects of applied therapy were assessed in 5 degree scale. The level of hemoglobin, the number of leucocytes, thrombocytes, bilirubine and transaminases in peripheral blood, hematurie, proteinurie, bleedings, appetite, nausea, vomitings, diarrhea, mucosal lesions, infections, skin lesions, cardiac lesions

  16. 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

  17. Clinical Research of Crizotinib in Advanced Non-small Cell Lung Cancer

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    Haibo ZHU

    2013-06-01

    Full Text Available At present, in the treatment of non-small cell lung cancer (NSCLC, targeted therapy has an important status. After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs, crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC. Phase I and II clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients, little side-effect, and well tolerated. Recently, crizotinib can inhibit ROS1 receptor tyrosine kinase and show extraordinary significant antitumor activity in ROS1-rearranged NSCLC. Drug resistance also exists in crizotinib. The mechanism of drug resistance needs further research. In this study, a review is performed in the mechanism and pharmacokinetics of crizotinib, and the clinical progress of treatment in advanced NSCLC.

  18. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A

    2015-04-01

    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

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

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    Gota V

    2014-06-01

    Full Text Available Vikram Gota,1 Krunal Kavathiya,1 Kartik Doshi,1 Murari Gurjar,1 Solai E Damodaran,1 Vanita Noronha,2 Amit Joshi,2 Kumar Prabhash2 1Department of Clinical Pharmacology, Advanced Centre for Treatment Research and Education in Cancer, 2Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India Background: 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. Methods: 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. Results: 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. Conclusion: Higher exposure to

  20. 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.

  1. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Antonelli, Giovanna; Libra, Massimo; Panebianco, Vincenzo; Russo, Alessia Erika; Vitale, Felice Vito; Colina, Paolo; D'Angelo, Alessandro; Rossello, Rosalba; Ferraù, Francesco

    2016-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib.

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

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    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

    To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC).Methods:A total of 89 patients with stage ⅢB or Ⅳ NSCLC received icotinib at a dose of 125 mg admimstered 3 times a day.Icotinib treatment was continued until disease progression or development of unacceptable toxicity.Results: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 (P<0.05).The symptom improvement rate was 57.3% (51/89),and the main symptoms improved were cough,pain,chest distress,dyspnea,and Eastern Cooperative Oncology Group performance status.The main toxic effects were rash [30/89 (33.7 %)] and diarrhea [15/89 (16.9%)].The level of toxicity was typically low.Conclusions:The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe,and its toxic effects are tolerable.

  4. Cetuximab Combination with Chemotherapy in Advanced Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-chun Duan; Lu Yang; Jie Wang; Jun Zhao; Mei-na Wu; Tong-tong An

    2009-01-01

    Objective: To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer (NSCLC), and to investigate the association of status of K-RAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome.Methods: Between Jan. 2006 and Sep. 2009, nineteen patients with advanced NSCLC received cetuximab (≥4 weeks) combined with chemotherapy in Department of Thoracic Oncology at Beijing Cancer Hospital. Response, survival and toxicity were retrospectively assessed, epidermal growth factor receptor (EGFR) protein expression was evaluated by ELISA Kit. The status of K-RAS gene mutation was tested by PCR-RFLP and EGFR gene amplification was measured by EGFR fluorescence in situ hybridization (FISH).Results: Partial response(PR) was observed in 26.3%(5/19) of the patients and stable disease(SD) in 52.6%(10/19). Median progression free survival(PFS) was 6 months (95% CI: 3.6-8.4). Median overall survival (MST) and 1-year survival rate(SR) were 10.6 months (95% CI: 6.6-14.6) and 47.6%, respectively. Mild or moderate skin rash was the most common toxicity related with cetuximab. K-RAS gene mutation, EGFR protein level and amplification have little correlation with prognosis.Conclusion: Cetuximab combined with chemotherapy was tolerable and the skin rash related with cetuximab was mild to moderate. Cetuximab may prolong survival of the patients who failed to previous chemotherapy.

  5. Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2007-01-01

    Full Text Available Beckground/Aim. Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC. Methods. A clinical trial included 158 patients (74% males and 26% females, with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion or chemotherapy only in stage III (with pleural effusion and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion, the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. Results. A total of 53 patients (34% had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively. Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.5%, 34 (21.5% and 33 (20.1% patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (p < 0.001; a two - year survival time noted in 30% of the patients (p = 0

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

    Science.gov (United States)

    González García, Jonathan; Gutiérrez Nicolás, Fernando; Nazco Casariego, Gloria Julia; Valcárcel Nazco, Cristina; Batista López, Jose Norberto; Oramas Rodríguez, Juana

    2017-01-01

    Introducción: El cáncer de pulmón es la tercera neoplasia tumoral más frecuente en España, con unos 27.000 nuevos casos/ año, de los que el 80-85% son de etiología no microcítica (NSCLC) y en la mayoría de los casos diagnosticados en estadíos avanzados de la enfermedad, razón por la que es uno de los procesos oncológicos con mayores tasas de mortalidad (supervivencia media a los 5 años del 21,4%). Los principales esquemas de primera línea utilizados en el tratamiento del NSCLC son: cisplatino/pemetrexed (cis/pem), cisplatino/gemcitabina/ bevacizumab (cis/gem/bev), y carboplatino/paclitaxel/bevacizumab (carbo/pac/Bev). El objetivo del presente trabajo consistirá en realizar un análisis para estimar el ratio coste-eficacia de los esquemas antineoplásicos de primera línea en el tratamiento del NSCLC, desde la perspectiva de la gerencia hospitalaria. Metodos: Se elaboró un modelo matemático de coste-eficacia basado en un árbol de decisiones. Como variable de eficacia se utilizó la supervivencia libre de progresión, obtenida de los ensayos clínicos fase III PARAMOUNT, AVAIL y SAIL. El estudio se efectuó desde la perspectiva de la gerencia hospitalaria considerando únicamente los costes directos de adquisición de los fármacos. Se realizó un análisis de sensibilidad determinístico para comprobar la robustez de los resultados. Resultados: La SLP obtenida en los ensayos clínicos de los tratamientos cis/pem, cis/gem/bev y carb/pac/bev fue de: 6,9, 6,7 y 6,2 meses, respectivamente. En base a nuestro modelo, el coste medio del tratamiento por paciente para estos esquemas fue de 19.942 €, 15.594 € y 36.095 €, respectivamente. La razón coste-eficacia incremenal por mes de SLP adicional entre cis/pem y cis/gem/bev fue de 19.303 €. Estimando una reducción del 30% de los costes de adquisición de pemetrexed (Alimta®Eli Lilly Nederland B.V) ante su próxima incorporación al mercado de medicamentos genéricos, el tratamiento cis/pem se convertiría en la alternativa dominante en el tratamiento de primera línea de los pacientes con NSCLC, al ofrecer los mejores resultados en salud a un menor coste.

  7. 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.

  8. The role of pembrolizumab in the treatment of advanced non-small cell lung cancer.

    Science.gov (United States)

    Santabarbara, Giuseppe; Maione, Paolo; Rossi, Antonio; Palazzolo, Giovanni; Gridelli, Cesare

    2016-06-01

    Lung cancer is the leading cause of death cancer related worldwide. The standard therapies have unmet medical needs both due to the limited activity and relevant toxicity of platinum-based chemotherapy and to the low frequency of specific alterations required to use targeted therapies. Immune checkpoint inhibition due to restoring the immune system's capacity to eradicate tumors is undergoing in extensive investigation in non-small cell lung cancer (NSCLC) as a new treatment approach. Programmed cell death protein-1 (PD-1) and its ligand, programmed cell death-ligand 1 (PD-L1) have recently led to significantly and durable improvements in the clinical outcome of several kind of tumors including lung cancer. Pembrolizumab, approved by the U.S. FDA for the treatment of advanced NSCLC progressed after other therapies and with expression of PD-L1, has demonstrated durable response and prolonged overall survival (OS) especially in patients with high PD-L1 expression. Further investigation are needed to improve treatment outcomes through combination of immunotherapy or combined with other targeted therapies.

  9. 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

    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......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...... for chemotherapy were enrolled in a prospective biomarker trial. A pre-treatment blood sample was drawn and subsequently DNA was extracted and pmKRAS analysed. The patients received carboplatin (AUC5) i.v. day 1 and vinorelbine (30mg/m(2) i.v. day 1 and 60mg/m(2) p.o. day 8) for a maximum of six cycles. Response...

  10. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    Science.gov (United States)

    Hong, Julian C; Salama, Joseph K

    2016-02-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors.

  11. Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Dolly, Saoirse O; Collins, Dearbhaile C; Sundar, Raghav; Popat, Sanjay; Yap, Timothy A

    2017-04-04

    Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival. However, the emergence of acquired resistance is inevitable. Novel potent compounds with much improved and rational selectivity profiles, such as third-generation EGFR T790M resistance mutation-specific inhibitors, have been developed and added to the NSCLC armamentarium. To date, attempts to overcome resistance bypass pathways through downstream signaling blockade has had limited success. Furthermore, the majority of patients still do not harbor known driver genetic or epigenetic alterations and/or have no new available treatment options, with chemotherapy remaining their standard of care. Several potentially actionable driver aberrations have recently been identified, with the early clinical development of multiple inhibitors against these promising targets currently in progress. The advent of immune checkpoint inhibitors has led to significant benefit for advanced NSCLC patients with durable responses observed. Further interrogation of the underlying biology of NSCLC, coupled with modern clinical trial designs, is now required to develop novel targeted therapeutics rationally matched with predictive biomarkers of response, so as to further advance NSCLC therapeutics through the next decade.

  12. CIMAvax-EGF: A New Therapeutic Vaccine for Advanced Non-Small Cell Lung Cancer Patients

    Science.gov (United States)

    Saavedra, Danay; Crombet, Tania

    2017-01-01

    Lung cancer is the common fatal illness with the highest incidence and mortality globally. Epidermal growth factor receptor overexpression by tumor cells is associated with uncontrolled proliferation, angiogenesis, anti-apoptotic signals, metastization, and invasiveness. CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and Montanide ISA 51, as adjuvant. The vaccine is projected to induce antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF demonstrated to be safe and immunogenic in advanced non-small cell lung cancer (NSCLC) patients. The efficacy study was an open-label, multicentric Phase III clinical trial, which enrolled 405 advanced NSCLC patients. Patients with proven stage IIIB/IV NSCLC, who had completed four to six cycles of chemotherapy (CTP) were randomized to receive CIMAvax-EGF or best supportive care. CIMAvax-EGF resulted in a significantly larger overall survival in patients receiving at least four doses. High EGF concentration at baseline was a good predictive biomarker of the vaccine activity and a poor prognostic biomarker for the non-treated population. The proportion of CD8+CD28− cells, CD4 cells, and the CD4/CD8 ratio after first-line CTP was also associated with CIMAvax-EGF clinical benefit. After completing the Phase III, a Phase IV trial was done where the vaccine was administered in primary care units. Administering the vaccine at primary care institutions granted better access and treatment compliance. Safety was confirmed. Several clinical trials are currently ongoing to validate EGF as a predictive biomarker of CIMAvax-EGF efficacy.

  13. Individualized dose prescription for hypofractionation in advanced non-small-cell lung cancer radiotherapy: an in silico trial.

    NARCIS (Netherlands)

    Hoffmann, A.L.; Troost, E.G.C.; Huizenga, H.; Kaanders, J.H.A.M.; Bussink, J.

    2012-01-01

    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 h

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

    Directory of Open Access Journals (Sweden)

    Kristine R. Jakobsen

    2015-03-01

    Full Text Available 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-derived vesicles displaying various proteins on their membrane surfaces. In addition, they are readily available in blood samples where they constitute potential biomarkers of human diseases, such as cancer. Here, we examine the potential of distinguishing non-small cell lung carcinoma (NSCLC patients from 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 analysis was capable of detecting and phenotyping exosomes in all samples from only 10 µL of unpurified plasma. Multivariate analysis using the Random Forests method produced a combined 30-marker model separating the two patient groups with an area under the curve of 0.83, CI: 0.77–0.90. The 30-marker model has a sensitivity of 0.75 and a specificity of 0.76, and it classifies patients with 75.3% accuracy. Conclusion: The EV Array technique is a simple, minimal-invasive tool with potential to identify lung cancer patients.

  15. Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer

    OpenAIRE

    Socinski, M A

    2014-01-01

    Based on demonstrated favourable risk–benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability c...

  16. Manifestation of leukoencephalopathy in a patient with advanced non-small cell lung cancer following treatment with gefitinib

    Institute of Scientific and Technical Information of China (English)

    HUANG Yi-sheng; HUANG Biao; WU Yi-long

    2011-01-01

    The present case is a patient with advanced non-small cell lung cancer (NSCLC) who developed leukoencephalopathy following radiotherapy and gefitinib treatments.There are rarely reports of such incidences because the median survival period of advanced NSCLC is only ten months.The features of leukoencephalopathy in this case were atypical for radiation leukoencephalopathy,so it was suspected that the leukoencephalopathy was associated with gefitinib.

  17. Recurrence patterns of advanced non-small cell lung cancer treated with gefitinib

    Institute of Scientific and Technical Information of China (English)

    CHEN Min-jiang; ZHONG Wei; ZHANG Li; ZHAO Jing; LI Long-yun; WANG Meng-zhao

    2013-01-01

    Background Gefitinib is widely used in the treatment of advanced non-small cell lung cancer (NSCLC).However,only a small number of reports have described initial failure sites in patients treated with gefitinib.The aim of this study was to investigate survival,recurrence sites,and treatment after recurrence in these patients.Methods A retrospective review was conducted of all patients with stage Ⅲ/Ⅳ NSCLC treated with gefitinib in Peking Union Medical College Hospital from October 2002 to September 2011.Patient characteristics,initial failure sites,associated clinical factors,and subsequent therapy were included in the analysis of prognostic factors.Results A total of 316 patients were identified The median progress free survival (PFS) and overall survival (OS) times were 238 days and 468 days,respectively.The median survival time after progression was 145 days.The sites of initial failure were lung (62.34%),bone (17.72%),central nerve system (CNS,16.14%),liver (9.49%),and others (7.19%).Patients with single-site progression or multi-site progression were 81.01% and 18.99%,respectively.Progression-free survival time was associated with lung and bone failure.Additionally,the median survival time after progression was lower in patients with multi-site progression and liver progression.Other initial failure sites displayed no relationship with survival,including CNS failure.Subsequent therapy may affect survival after progression.In patients receiving continuous epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy,chemotherapy,radiotherapy,and retreatment with EGFR-TKIs,survival time after progression was prolonged compared with the best supportive care.Conclusions Our data suggest that patients receiving gefltinib should be closely monitored regarding lung metastasis during follow-up.Liver metastases and multi-site progression were poor prognostic factors.After failure with gefltinib,patients may benefit from radiotherapy

  18. The cost of treating advanced non-small cell lung cancer: estimates from the chinese experience.

    Directory of Open Access Journals (Sweden)

    Xiaohui Zeng

    Full Text Available BACKGROUND: Because of the potentially significant economic burden of healthcare costs associated with many diseases, it is critical that regulatory and medical insurance organisations collect and utilise data on the cost-effectiveness of care provision to make rational policy decisions. However, little is known about healthcare costs in China. METHODOLOGY/PRINCIPAL FINDINGS: Based on health expenditure data for 253 cases of advanced non-small cell lung cancer (NSCLC registered at the Second Xiangya Hospital of Central South University in China between 2006 and 2010, the cost of care provision was analysed. The monthly and aggregate annual medical costs were estimated for patients who were in either a progression-free state (PFS or a disease-progression state (DPS. Monthly healthcare costs accumulated during the terminal 3 months were collected separately. The mean cost of treatment for PFS and DPS patients over one year was approximately US$11,566 and $14,519, respectively. The monthly costs for all patients were higher initially than in the subsequent months (PFS: $2,490; DPS: $2,503. For PFS patients, healthcare expenditures stabilised after the 7th month, with a mean monthly medical expenditure of $82.49. For DPS patients, expenditures stabilised after the 9th month, and the mean expenditure during the 9th month was $307.9. Medical care costs in the three successive months prior to death were $3,754, $5,829 and $7,372, respectively. CONCLUSIONS/SIGNIFICANCE: The economic evaluation of health care technologies is becoming ever more important in China, especially in disease areas for which new and expensive therapies are being introduced on a regular basis. This is first paper to present empirically estimated China-specific costs associated with the treatment of NSCLC. The cost estimates are presented in a format that is specifically intended to inform cost-effectiveness analyses of treatments for NSCLC, and hence, contribute to the more

  19. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer

    OpenAIRE

    Antonelli,Giovanna; Libra, Massimo; PANEBIANCO, VINCENZO; Russo,Alessia Erika; Vitale, Felice Vito; COLINA, PAOLO; D'Angelo,Alessandro; ROSSELLO, ROSALBA; Ferraù, Francesco

    2015-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared wit...

  20. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation

    Directory of Open Access Journals (Sweden)

    Vijay M. Patil

    2016-01-01

    Full Text Available Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years. Grades 3-4 toxicity with NACT were seen in 19 patients (76%. The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48% patients and radical chemoradiation in 9 (36% patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort.

  1. Advances of Driver Gene and Targeted Therapy of Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Dan ZHANG

    2014-10-01

    Full Text Available Lung cancer is the leading cause of cancer-related mortality in the worldwide. The discovery of drive gene makes tumor treatment is no longer "one-size-fits-all". Targeted therapy to change the present situation of cancer drugs become "bullet" with eyes, the effect is visible and bring a revolution in the treatment of lung cancer. The diver gene and targeted therapy have became the new cedule of non-small cell lung cancer (NSCLC. Society of Clinical Oncology (ASCO has showed 11 kinds of diver genes. Here, we review the functional and structural characteristics and the targeted therapy in the 11 kinds of driver gene mutations.

  2. [Advances of driver gene and targeted therapy of non-small cell lung cancer].

    Science.gov (United States)

    Zhang, Dan; Huang, Yan; Wang, Hongyang

    2014-10-20

    Lung cancer is the leading cause of cancer-related mortality in the worldwide. The discovery of drive gene makes tumor treatment is no longer "one-size-fits-all". Targeted therapy to change the present situation of cancer drugs become "bullet" with eyes, the effect is visible and bring a revolution in the treatment of lung cancer. The diver gene and targeted therapy have became the new cedule of non-small cell lung cancer (NSCLC). Society of Clinical Oncology (ASCO) has showed 11 kinds of diver genes. Here, we review the functional and structural characteristics and the targeted therapy in the 11 kinds of driver gene mutations.

  3. Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Meko, J; Rusch, V W

    2000-10-01

    During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

  4. 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.

  5. Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer.

    Science.gov (United States)

    Socinski, M A

    2014-10-01

    Based on demonstrated favourable risk-benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability compared with solvent-based paclitaxel-carboplatin in a phase iii trial. This review focuses on the evolution of first-line taxane therapy for advanced nsclc and the new options and advances in taxane therapy that might address unmet needs in advanced nsclc.

  6. A retrospective analysis of efficacy and safety of adding bevacizumab to chemotherapy as first- and second-line therapy in advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Quan, Rencui; Huang, Jiaxing; Chen, Nan; Fang, Wenfeng; Hu, Zhihuang; Zhan, Jianhua; Zhou, Ting; Zhang, Li; Zhang, Hongyu

    2016-08-01

    Several phase III clinical trials had authenticated that the addition of bevacizumab to paclitaxel plus carboplatin or gemcitabine plus cisplatin showed encouraging efficacy as first-line therapy for advanced NSCLC patients. However, the benefits of adding bevacizumab to other chemotherapy regimens in first- or second-line therapy have not been reported. To compare the clinical efficacy and safety of bevacizumab concomitant with chemotherapy regimens in patients with advanced NSCLC as first- or second-line therapy, we retrospectively reviewed the effects of adding bevacizumab to chemotherapy regimens in naive-chemotherapy and pre-chemotherapy patients with advanced non-squamous NSCLC. A total of 79 patients with advanced non-squamous NSCLC received at least two cycles of bevacizumab with chemotherapy between October 2010 and December 2013 were selected. Our primary end points were overall response rate (ORR) and disease control rate (DCR). The secondary objective was overall survival (OS) and safety. Seventy-nine patients were included in this study. Overall response rates at first evaluation (after 2 cycles) were 23.1 % (9/39) and 5.0 % (2/40) in first- and second-line therapy (P = 0.020), respectively. And disease control rates were 84.6 % (33/39) and 50 % (20/40), respectively (P = 0.001). The median OS were 27.2 months (95 % CI 13.3-41.1 months) and 29.6 months (95 % CI 6.7-52.5 months), respectively (P = 0.740). Grade 3-4 adverse events included leukopenia (2/39), and neutropenia (3/39) in first-line therapy versus neutropenia (1/40) and thrombocytopenia (2/40) in second-line treatment. In our experience, combination of bevacizumab and chemotherapy had encouraging anti-tumor efficacy as both first- and second-line therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

    OpenAIRE

    White, S. C.; Lorigan, P; MARGISON, G. P.; Margison, J M; Martin, F.; Thatcher, N.; Anderson, H; Ranson, M.

    2006-01-01

    To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0–2. The first cohort received SPI-77 at 100 mg m−2, the second 200 mg m−2 and the final cohort 260 mg m−2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six pat...

  9. First- and second-line treatment of advanced metastatic non-small-cell lung cancer: a global view

    Directory of Open Access Journals (Sweden)

    Thatcher Nicholas

    2008-09-01

    Full Text Available Abstract Treatment of non-small-cell lung cancer is dependent on disease stage. For patients with metastasis or locally advanced disease, the importance of finding therapeutic schemes that may benefit this population is important. This review discusses therapeutic options for first- and second-line treatment in patients with advanced non-small-cell lung cancer. According to current data, the combination of two cytotoxic agents is the optimum first-line treatment for patients with non-small-cell lung cancer and performance status of 0–1. Addition of bevacizumab has shown to provide an even longer survival and to increase response rate. Within the first-line setting, erlotinib appears to be effective in the treatment of elderly patients who would not derive a benefit from standard chemotherapy or those refusing standard chemotherapy. The administration of erlotinib as first-line maintenance therapy is being assessed. There are currently three drugs approved for second-line treatment of patients with advanced non-small-cell lung cancer after failure of first-line chemotherapy. These drugs have proven to be effective in phase III trials. In the phase III trial BR.21 study, the response rate was 8.9% in the erlonitib group, and less than 1% in placebo; median response duration was 7.9 months and 3.7 months, respectively; and the median survival was 6.7 months and 4.7 with erlotinib and placebo, respectively. One-year survival was 31% and 21% with erlotinib and placebo, respectively. In addition, the BR.21 trial revealed that significantly greater improvements in overall quality of life and in both physical and emotional functioning were observed in the erlotinib arm as compared with the placebo arm. Erlotinib is not significantly associated with hematologic adverse effects. Erlotinib is administered orally, and does not require concomitant administration of other drugs, thus causing patients less inconvenience. Analysis of data from different

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

    DEFF Research Database (Denmark)

    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...... radiotherapy (IMRT) and concomitant chemotherapy (CCT). METHODS: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC were treated in a multicenter randomized phase II trial with 2 cycles of induction chemotherapy followed by IMRT and CCT. The esophagitis was prospectively scored using the Common...

  11. Clinical Observation of Erlotinib in the Treatment of Advanced and Previously Treated Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Liyan XU

    2009-12-01

    Full Text Available Background and objective Erlotinib is a small molecular inhibitor of tyrosine kinase. One study has confirmed that it can prolong the median progression-free survival time (PFS, and can improve the one-year survival rate of patients with advanced non-small cell lung cancer. The aim of this trial is to evaluate the response and adverse reaction of agent erlotinib in advanced and previously treated non-small-cell lung cancer. Methods The study was one part of the EAP (Expanded Access Programme study. Forty-five patients with advanced non-small cell lung cancer, which had been treated with 1-2 regimens containing platinum previously, were treated with erlotinib from Dec 2005. Erlotinib was prescribed at a dose of 150 mg daily. Results Forty-three patients were evaluated response and all patients were evaluated toxicity. Among these patients, CR 0 case, PR 19 cases (44.2%, RR (CR+PR 44.2% and SD 13 cases as their best response, disease control rate (DCR=CR+PR+SD 74.4%, PD 11cases (25.6%. The median progression-free survival time was 4.8 months; the median survival time was 15.0 months; the one-year survival rate was 68.8% (31/45. The median PFS of patients with adenocarcinoma and with non-adenocarcinoma was 7.6 months vs 2.6 months (P=0.018. The drug-related adverse reactions were skin rash (41 cases, 91.1%, billirubine increased (15 cases, 33.3%, ALT increased (9 cases, 20% and diarrhea (4 cases, 8.9%. For patients with and without skin rash, the median PFS was 7.5 months vs 1.1 months (P=0.001, and the median survival time was 15.6 months vs 5.2 months (P=0.002. Conclusion Erlotinib is effective in advanced and previously treated non-small cell lung cancer, and it is much more effective in adenocarcinoma and patients with skin rash. It is well tolerated, only with some minimal adverse reactions.

  12. New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib

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    Rothschild SI

    2016-05-01

    Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%–8% of non-small-cell lung cancer (NSCLC patients. Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial. Despite the initial treatment response of crizotinib, disease progression inevitably develops after approximately 10 months of therapy. Different resistance mechanisms have recently been described. One relevant mechanism of resistance is the development of mutations in ALK. Novel ALK tyrosine kinase inhibitors have been developed to overcome these mutations. Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naïve ALK-positive disease. In this paper, preclinical and clinical data of ceritinib are reviewed, and its role in the clinical setting is put into perspective. Keywords: lung cancer, ALK, ceritinib, crizotinib

  13. 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.

  14. EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH CARBOPLATIN ON ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    XIONG Hong-chao; CHEN Jin-feng; ZHANG Li-jian

    2006-01-01

    Objective: To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer (NSCLC). Methods: Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results: Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion: Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.

  15. Clinical efficacy evaluation of Liujunzi decoction combined with EP chemotherapy regiment for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xin-Jun Xiong; Long-Jun Xiong

    2016-01-01

    Objective:To analyze the clinical efficacy of Liujunzi decoction combined with EP chemotherapy regiment for advanced non-small cell lung cancer.Methods:A total of 72 cases of patients with non-small cell lung cancer were included in the study, the range of patients’ treatment was from August 2012 to October 2014, and according to different treatment, they were divided into observation group 36 cases and control group 36 cases. Control group received EP chemotherapy, observation group received Liujunzi decoction combined with EP chemotherapy regiment, and then differences in serum tumor marker levels, tumor tissue-related protein levels, PDCD5, Nrf2, HIF-1α and GLUT1 levels, and levels of VEGF, GSTs, TSGF and so on were compared between two groups.Results:Serum CY211, SCC, NSE, CEA and CA199 levels of observation group after treatment were lower than those of control group; TUBB3, ERCC-1, MT and P53 expression levels of observation group after treatment were lower while Mcll and Fbw7 expression levels were higher; PDCD5 level of observation group after treatment was higher than that of control group while Nrf2, HIF-1α and GLUT1 levels were lower than those of control group; CD4+CD25+Foxp3+ Treg/CD4+ T, VEGF, GSTs and TSGF values of observation group after treatment were lower than those of control group. Conclusion:Liujunzi decoction combined with EP chemotherapy regiment for patients with advanced non-small cell lung cancer can effectively inhibit tumor cell proliferation as well as invasion and metastasis, is helpful for disease control and prognosis improvement, and has positive clinical significance.

  16. Effect of nimotuzumab targeted therapy combined with conventional chemotherapy in treatment of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Ping Xu; Hui-Juan Wu; Shang-Shuang Shi

    2016-01-01

    Objective:To study the clinical efficacy of nimotuzumab targeted therapy combined with conventional chemotherapy in treatment of advanced non-small cell lung cancer.Methods:Patients with non-small cell lung cancer were selected for study and randomly divided into targeted group and conventional group, efficacy of two groups after 2 and 4 treatment cycles was evaluated, tumor tissue was collected and activation of PI3K/AKT pathway, MAPK/ERK pathway and JAK2/STAT3 pathway was detected.Results:After 2 and 4 chemotherapy cycles, CR case number, PR case number and SD case number of targeted group were significantly more than those of conventional group (P<0.05); PD case number was significantly less than that of conventional group (P<0.05). Expression levels of PI3K, AKT, MAPK, ERK1, ERK2, JAK2 andSTAT3 in tumor tissue of targeted group were significantly lower than those of conventional group (P<0.05). Expression levels of FasL and Bim in tumor tissue of targeted group were significantly higher than those of conventional group (P<0.05), and expression levels ofBcl-2, Survivin, VEGF, HIF-1α andEPO were significantly lower than those of conventional group (P<0.05).Conclusions:Nimotuzumab targeted therapy combined with conventional chemotherapy can achieve more precise short-term efficacy and inhibit the activation of PI3K/AKT pathway, MAPK/ERK pathway and JAK2/STAT3 pathway, and it is a more ideal solution for treatment of advanced non-small cell lung cancer.

  17. [Clinical application value of prognostic nutritional index for predicting survival in patients with advanced non-small cell lung cancer].

    Science.gov (United States)

    Xu, W J; Kang, Y M; Zhou, L; Chen, F F; Song, Y H; Zhang, C Q

    2017-02-23

    Objective: To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: 123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC. Results: PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001). Conclusion: PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.

  18. VINDESINE WITH CYCLOPHOSPHAMIDE-EPIRUBICIN-CISPLATIN IN THE TREATMENT LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    HU Yan-ping; KE Yu-hua; FU Xiao-yu

    1999-01-01

    Objective: To evaluate the addition of vindesine to a cyclophosphamide-epirubicin-cisplatin (CAP) regimen for treating the patients with locally advanced non-small cell lung cancer (NSCLC). Methods: From May 1994to August 1998, 59 previously untreated patients with stage Ⅲa and Ⅲb non-small cell lung cancer were enrolled into this trial. Patients characteristics were the following: the median age was 52 years; the median performance status was 1; there were 19 stage Ⅲa and 40 stage Ⅲb; there were 47 adenocarcinoma, 10squamous cell carcinoma and 2 large cell carcinoma. All patients were treated with vindesine (2 mg/m2, on day 1and day 8), cyclophosphamide (0.6/m2, on day 1),epirubicin (40 mg/m2, on day 1) and cisplatin (60 mg/m2,on day 1) every 3 or 4 weeks. Results: Four achieved a complete response (6.8%), 29 achieved a partial response (49.2%), 15 had stable disease, and 10 had progressive disease. A clinical improvement was in 45 of 59 patients (76.3%). The most frequent major toxic effects were myelosuppression, nausea and vomiting.Conclusion: The vindesine with CAP regimen was active combination chemotherapy in patients with locally advanced NSCLC accompanied by the limited side effects.

  19. Effect of vinorelbine, ifosfamide, and cisplatin combination chemotherapy in advanced non-small-cell lung cancer.

    Science.gov (United States)

    Ahn, J B; Ko, W K; Lee, J G; Shim, K Y; Jeung, H C; Park, J O; Yoo, N C; Kim, B S; Kim, S K; Kim, S K; Kim, J H

    2000-12-01

    Cisplatin-based chemotherapy is being tried in the treatment of nonoperable cases of non-small-cell lung cancer (NSCLC). However, the prognosis is unfavorable and to improve survival, clinical studies using various combinations of a variety of drugs as well as experimental material are in progress. We compared the efficacy and toxicities of combination chemotherapy using different doses of vinorelbine and ifosfamide with a constant dose of cisplatin in this study. Patients diagnosed with inoperable stage III or IV NSCLC between June 1997 and December 1998 were included. Cisplatin was administered at a constant dose of 80 mg/m2 on day 5, whereas vinorelbine on days 1 and 5 and ifosfamide on day 5 were administered in one of two different doses. In arm A, vinorelbine 25 mg/m2 and ifosfamide 3.0 g/m2 were administered. In arm B, vinorelbine 20 mg/m2 and ifosfamide 2.5 g/m2 were administered. Also, we reviewed for phase II and III studies that test 1) cisplatin, 2) vinorelbine monotherapy, and 3) vinorelbine/cisplatin/ifosfamide combination chemotherapy for stage IIIb-IV non-SCLC. Summation dose intensity (SDI) was calculated in each published and current study. Twenty patients in arm A and 35 patients in arm B were available for evaluation. There was no difference in patient activity, pathologic diagnosis, and differentiation or stage between the two arms. The median number of cycles was four in both arms. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A and B were 40 and 42 weeks, respectively, whereas the SDI was 1.94 and 1.7, respectively. More than grade III leukopenia was observed in 28.9% in arm A, which is more frequent than the 17.2% in arm B. There was a significant correlation between the SDIs and response rates and median survival (r2 = 0.629, p = 0.001; r2 = 0.453, p = 0.001, respectively). Although the follow-up period is relatively short, the survival time was similar in both arms. Because a high response rate may

  20. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Zhenzhen eHui

    2015-12-01

    Full Text Available We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus cytokine-induced killer cells.

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

    DEFF Research Database (Denmark)

    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...

  2. The efficacy and safety of pemetrexed-based doublet therapy compared to pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer: an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhong AY

    2015-07-01

    Full Text Available Anyuan Zhong,1* Xiaolu Xiong,2* Minhua Shi,1 Huajun Xu3 1Department of Respiratory Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, 2Department of Endocrinology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, 3Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contribute equally to this work Background: Pemetrexed is currently recommended as the second-line treatment for patients with advanced non-small-cell lung cancer (NSCLC. However, it is unclear whether pemetrexed-based doublet therapy improves treatment efficacy and safety. Thus, this meta-analysis was performed to resolve this controversial question. Methods: Electronic databases, including PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant articles before April 2015. Hazard ratios (HRs were used to estimate overall survival (OS and progression-free survival (PFS, and odds ratios (ORs were used to analyze the overall response rate (ORR and grade ≥3 toxicities. Subgroup analysis, sensitivity analysis, and publication bias were also evaluated. Results: A total of 2,519 patients from ten randomized controlled trials were included. Compared to pemetrexed alone, PFS and ORR significantly improved in the pemetrexed-based doublet group (HR, 0.86; 95% CI [confidence interval], 0.75–0.99; P=0.038; and OR, 1.98; 95% CI, 1.25–3.12; P=0.003, respectively. However, no statistically significant differences in OS were observed between groups (HR, 0.92; 95% CI, 0.83–1.02; P=0.132. In addition, subgroup analyses indicated that improved OS was only observed in nonsquamous NSCLC patients who received the combination of pemetrexed and erlotinib. An increasing incidence of grade ≥3 neutropenia and thrombocytopenia was observed in the pemetrexed

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    von Plessen, Christian

    2011-01-01

    treatment option is palliative chemotherapy. Given the palliative intention of the chemotherapy, it is clinically highly relevant to establish the optimal treatment duration. While chemotherapy prolongs survival and improves quality of life (QoL), it also has side effects and only a minority of patients...... achieve an objective treatment response. Clinicians need guidance on treatment duration from controlled trials to balance these aspects. Improvements of the conditions under which chemotherapy is given can increase patient and staff satisfaction and increase system performance. This is especially relevant...... of care. Clinicians, health care administrators and the public need knowledge about the outcomes of palliative chemotherapy in unselected patient populations. The efficacy of palliative chemotherapy for advanced NSCLC has been amply documented in controlled clinical trials. Meanwhile, the elderly...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Current Research on Consolidation Therapy and Follow-up Health Care in Advanced Non-small Cell Lung Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    Runbo Zhong; Baohui Han; Bo Jin

    2008-01-01

    ABSTRACT Following concurrent radio-chemotherapy or first-line chemotherapy for advanced non-small cell lung cancer(NSCLC), continuous maintenance therapy given to patients with stable disease (SD) and follow-up treatment is called consolidation therapy. Concerning NSCLC patients with a non-operable dry Stage-ⅢB (N3) disease, I.e. Contra-lateral mediastinal and hilar lymph node, or homolateral/contra-lateral scalene and Troisier sign, a 2 or 3-course of standard-dosage Taxotere consolidation therapy can be performed after concurrent radio-chemotherapy. In pursuance of evidence-based medicine (EBM), low-dose Taxoteremaintenance therapy, and biological targeted therapy of patients with appropriate symptoms are suitable for second-line therapy for moist of the Stage-ⅢB (malignant pleural effusion) and Ⅳpatients.

  7. 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-derived vesic......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...

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

    DEFF Research Database (Denmark)

    Jakobsen, Kristine R; Paulsen, Birgitte S; 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-derived vesic......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...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Vinorelbine plus Oxaliplatin versus Vinorelbine plus Cisplatin for Advanced Non-small Cell Lung Cancer: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Kehu YANG

    2010-02-01

    Full Text Available Background and objective Cisplatin (DDP plus vinorelbine (NVB constitute the first-line regimen (NP regimen for non-small cell lung cancer (NSCLC. Oxaliplatin (OXA is another effective drug in treatment of NSCLC with mild toxicities to gastrointestinal tract, kidney and bone marrow. The aim of this study is to evaluate the efficiency and safety between NVB plus OXA (NO regimen and NP regimen for advanced NSCLC. Methods We searched CBM, CNKI, VIP, Cochrane Library, PubMed, EMBASE, ASCO etc. conference proceedings and internet information. Randomized controlled trials of NO versus NP for advanced NSCLC were included; we evaluated the quality of the included studies and analyzed data by Cochrane Collaboration’s RevMan 5.0 software. Results Fourteen randomized trials involving 1 270 patients were included. There were no statistical differences between NO and NP in overall response rate, disease control rate, 1-year survival rate, anemia and thrombocytopenia. Gastrointestinal toxicity, leucopenia, alopecia and kidney toxicity were more serious in NP (P < 0.05, but neuritis was more serious in NO, with significant difference (P <0.05. Conclusion The clinical efficacy of NO and NP for advanced NSCLC was similar, but the side effects were different. The toxicity of NO has the tendency to be more tolerable.

  11. Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Pu-Yuan Xing; Jun-Ling Li; Yan Wang; Xue-Zhi Hao; Bin Wang; Lin Yang; Yuan-Kai Shi

    2013-01-01

    Objective:To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC).Methods:We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010.The treatment-related survival was also analyzed.Results:Of these 21 patients,the best overall response was partial response (PR) in 6 patients (28.6%),stable disease (SD) in 10 patients (47.6%),and progressive disease (PD) in 5 patients (23.8%).The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%.The median progression-free survival (PFS) was 4.0 months (95% CI,5.0-7.0 months).The main grade 3/4 toxicities included neutropenia (11.1%),peripheral nerve toxicity (5.6%),muscle and joint aches (5.6%),and fatigue (5.6%).Conclusions:The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.

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

    Science.gov (United States)

    Guetz, Sylvia; Tufman, Amanda; von Pawel, Joachim; Rittmeyer, Achim; Borgmeier, Astrid; Ferré, Pierre; Edlich, Birgit; Huber, Rudolf Maria

    2017-01-01

    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 days and only marginal accumulation. The tolerability profile was acceptable (all dose levels – all grades: decreased appetite 33%, diarrhea 33%, leukopenia 33%, nausea 30%, vomiting 26%; ≥grade 3: leukopenia 30%, lymphopenia 19%, neutropenia 19%, febrile neutropenia 15%). Disease control rate, OS and TTP signaled a treatment effect. Conclusion Daily metronomic NVBo therapy in extensively pretreated patients with advanced NSCLC is feasible and safe at the recommended dose of 30 mg/d. Escalation to 40 mg/d in the second cycle is possible. The blood concentrations of vinorelbine after daily metronomic dosing reached lower peaks than intravenous or oral conventional

  13. New targeted treatments for non-small-cell lung cancer – role of nivolumab

    Science.gov (United States)

    Zago, Giulia; Muller, Mirte; van den Heuvel, Michel; Baas, Paul

    2016-01-01

    Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017) and non-squamous NSCLC (CheckMate 057). In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively). Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. PMID:27536062

  14. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond

    Directory of Open Access Journals (Sweden)

    Alexander eChi

    2014-06-01

    Full Text Available Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-PET incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

  15. Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Platinum-based chemotherapy can improve the survival and quality of life of patients with locally advanced and metastatic lung cancer. Second-line docetaxel monotherapy can improve overall survival following the failure of first line chemotherapy. However, many limiting factors such as poor performance status, advanced age, adverse effects of chemotherapy and reluctance to receive cytotoxic chemotherapeutic agents render patients unable to accept chemotherapy. Furthermore, for patients who have failed second-line chemotherapy treatment options are often limited to best support care or palliative radiotherapy. 1 Gefitinib (Iressa) is a HER1/EGFR (epidermal growth factor receptor)- tyrosine kinase inhibitor approved in a number of countries including the US, Japan and recently China for the treatment of patients with non-small cell lung cancer (NSCLC), who have failed platinum/docetaxel-based first line and second line chemotherapy. 2,3 Current data show heterogeneity in response to gefitinib among people of different ethnic origin, but there is very little data concerning the safety and efficacy of gefitinib in Chinese patients. This paper aims to summarize the safety and efficacy data for gefitinib 250 mg treatment in Chinese NSCLC patients at Peking Union Medical College Hospital who received gefitinib as part of an Expanded Access Programme.

  16. Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

    Science.gov (United States)

    Manegold, Christian

    2014-09-01

    The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources.

  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. Association between different EGFR mutation status and survival in pemetrexed-based chemotherapy for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    郏博

    2014-01-01

    Objective To explore the association between different epidermal growth factor receptor(EGFR)mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer(NSCLC).Methods A retrospective cohort study was performed to assess146 patients with advanced NSCLC at Cancer

  19. Phase I study of docetaxel and irinotecan in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Nogami, Naoyuki; Harita, Shingo; Ueoka, Hiroshi; Yonei, Toshiro; Kiura, Katsuyuki; Kamei, Haruhito; Tabata, Masahiro; Segawa, Yoshihiko; Gemba, Kenichi; Tanimoto, Mitsune

    2004-07-01

    The role of non-platinum combination chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has not yet been clarified. In this phase I study, the dose-limiting toxicity (DLT), the maximum tolerable dose (MTD) and the antitumor activity of a two-drug combination of docetaxel (DCT) and irinotecan (CPT) in patients with advanced NSCLC were evaluated. Previously untreated patients with NSCLC in stage IIIB with malignant pleural effusion or stage IV were eligible. Both drugs were administered by 1-h intravenous infusion on day 1, and repeated every 3 weeks. DCT was given before CPT administration. Five escalating dose levels of DCT/CPT (40/135, 50/135, 50/150, 60/150, and 60/165 mg/m2) were studied. Eighteen patients received 44 courses. The DLT was considered to be neutropenia, because grade 4 neutropenia lasting for 3 days or more was observed in three patients, which was accompanied with three episodes of febrile neutropenia. As a non-hematological toxicity, grade 3 diarrhea occurred in three patients. Since all the three patients treated at the fifth dose level (DCT at 60 mg/m2 and CPT at 165 mg/m2) experienced DLT (grade 4 neutropenia in two patients and grade 3 hepatic toxicity in one), this dose level was determined to be the MTD. The objective response rate was 33.3%, and the median survival time was 13.6 months. To confirm the effectiveness of this combination for advanced NSCLC which was suggested in the present study, a phase II study with the recommended doses (150 mg/m2 for CPT and 50-60 mg/m2 for DCT) is warranted.

  20. Clinical analysis of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Qianping Li; Jianjun Wang; Jun Zhang; Chengyi Lin

    2012-01-01

    Objective: The purpose of this study was to assess the curative effect and adverse reaction of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer (NSCLC). Methods: This prospective randomized controlled trial included 115 patients with locally advanced NSCLC were randomly divided into experimental and control groups and were treated from January 2007 to January 2010. The experimental group of 63 cases was treated with two cycles of induction chemotherapy before operation, radical surgery had been performed about three weeks after completion of chemotherapy, followed by received two cycles of chemotherapy. And the control group (52 cases) was treated at first with radical surgery, then treated with four cycles of chemotherapy. Two groups of the cases received routine thoracic radiotherapy with a total dose of 45 Gy. One cycle of gemcitabine combined with cisplatin regimen in-cluded gemcitabine 1000 mg/m2 on day 1 and day 8 and cisplatin 25 mg/m2 on day 1, day 2 and day 3 by intravenous infusion, with 21 days as one cycle. The tumor recurrence was evaluated by chest CT and abdominal B-ultrasound. Efficacy and toxicity results were compared by two groups. Results: All patients were followed up for three months to two years. The surgical stage of the experimental group reduced, two-years disease-free survival and postoperative recovery in the experimental group were better than in the control group, the difference was statistical significant. Toxicity and side effect after chemotherapy were mainly bone marrow suppression and gastrointestinal reactions, other complications included thrombocytopenia, leuko-penia, anemia, liver and kidney dysfunction were no significant difference in two groups. Conclusion: Preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced lung cancer can reduce the surgical staging and extend the postoperative disease-free survival.

  1. 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.

  2. Phase II Trial of Improved Regimen with Gemcitabine in Patients 
with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lulu MIAO

    2012-01-01

    Full Text Available Background and objective Gemcitabine-platinum-combined with chemotherapy is the most common treatment for advanced non-small cell lung cancer (NSCLC. Gemcitabine is administered once a week in a general three-week schedule. In the present study, gemcitabine is administered on d1 and d5 to improve compliance, and the efficacy and safety of the improved regimen is evaluated in untreated patients with advanced NSCLC. Methods A total of 83 patients were enrolled between October 2007 and October 2009. In each cycle, gemcitabine was administered at a dose of 1,000 mg/m2-1,250 mg/m2 via a 30 min intravenous infusion on d1 and d5 followed by cisplatin at a dose of 75 mg/m2 or carboplatin (AUC=5 on d1 every three weeks. At least two cycles of chemotherapy were completed in each case, and clinical response and toxicity of the regimen were observed. Results The objective response rate was 37.3%. The median progression free survival and overall survival time were 6.1 months and 15.0 months, respectively. The one-year and two-year survival rates were 57.8% and 16.2%, respectively. Myelosuppression and gastrointestinal responses were the main toxicities. The incidence of grade 3/4 of leucopenia, hypohemia, and thrombocytopenia were 26.5%, 10.8% and 7.2%, respectively. A total of 27.5% of the patients in the cisplatin group had grade 3/4 gastrointestinal responses. Treatment related deaths were not observed in this study. Conclusion The regimen is active and well-tolerated in untreated patients with advanced NSCLC. Further randomized controlled studies are necessary.

  3. Treatment of Unfit Patients With Advanced Non-Small-Cell Lung Cancer: Definition Criteria According an Expert Panel.

    Science.gov (United States)

    De Marinis, Filippo; Bria, Emilio; Baas, Paul; Tiseo, Marcello; Camerini, Andrea; Favaretto, Adolfo Gino; Gridelli, Cesare

    2015-11-01

    The assessment of special categories of non-small-cell lung cancer (NSCLC) patients requires a comprehensive analysis of all factors potentially influencing the daily quality of life and the relative contribution of tumor-related symptoms on the overall patient health status. While for elderly patients prospective evidence and recommendations allow clinicians to better address their patients to a shared treatment, a paucity of reliable data refers to treatment opportunities for these patients, termed frail or unfit, who are not considered eligible for chemotherapy usually administered to adult patients. This consensus was inspired by the absence of clear criteria to define the category of unfit patients in the context of advanced NSCLC in order to share all the available tools for their classification and evaluation and to support decisions for clinical practice on a daily basis. After review of the literature and panelist consensus, a series of items was identified as relevant: age, performance status, renal function, heart failure, previous cerebrovascular events, uncontrolled hypertension, neuropathy, hearing loss, symptomatic brain metastases, severe psychiatric disorders, and absence of caregiver support. On the basis of these factors, a treatment algorithm for clinical practice to categorize unfit NSCLC patient into 3 major clinical scenarios was defined: (1) unfit for cisplatin-based chemotherapy, (2) unfit for carboplatin-based chemotherapy, and (3) unfit for single-agent chemotherapy.

  4. 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

  5. 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.

  6. Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer.

    Science.gov (United States)

    White, S C; Lorigan, P; Margison, G P; Margison, J M; Martin, F; Thatcher, N; Anderson, H; Ranson, M

    2006-10-09

    To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0-2. The first cohort received SPI-77 at 100 mg m-2, the second 200 mg m-2 and the final cohort 260 mg m-2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m-2 dose level for an overall response rate of 4.5% (7.1% at >or=200 mg m-2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.

  7. Afatinib: a review of its use in the treatment of advanced non-small cell lung cancer.

    Science.gov (United States)

    Keating, Gillian M

    2014-02-01

    Afatinib (Gilotrif™, Giotrif(®)) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. Afatinib downregulates ErbB signalling by covalently binding to the kinase domains of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER) 2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation; it also inhibits transphosphorylation of HER3. Afatinib is approved as monotherapy for the treatment of EGFR tyrosine kinase inhibitor (TKI)-naïve adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutations in the EU, and for the first-line treatment of patients with metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a US FDA-approved test in the US. In two randomized, open-label, multinational phase III trials, progression-free survival was significantly prolonged with afatinib compared with pemetrexed plus cisplatin (LUX-Lung 3) or gemcitabine plus cisplatin (LUX-Lung 6) in treatment-naïve patients with advanced NSCLC with activating EGFR mutations. The objective response rate was significantly higher with afatinib than with pemetrexed plus cisplatin or gemcitabine plus cisplatin, and patient-reported outcomes for symptoms such as cough and dyspnoea and certain health-related quality of life measures significantly favoured afatinib versus pemetrexed plus cisplatin or gemcitabine plus cisplatin. Afatinib also showed efficacy in EGFR TKI-naïve patients with advanced lung adenocarcinoma and activating EGFR mutations who had received no more than one prior chemotherapy regimen for advanced disease, according to the results of the noncomparative, multinational, phase II LUX-Lung 2 trial. Oral afatinib had a manageable tolerability profile. EGFR-mediated adverse events (e.g. diarrhoea, rash/acne) were generally managed using dose reduction and delays. In conclusion, afatinib

  8. Survival Analysis of Advanced Non-Small Cell Lung Cancer Patients Treated by Using Wheel Balance Cancer Therapy.

    Science.gov (United States)

    Kim, Jongmin; Cho, Chong-Kwan; Yoo, Hwa-Seung

    2016-12-01

    Objective To investigate the clinical effect and the overall survival (OS) rate of patients with advanced non-small cell lung cancer (NSCLC) who have undergone Wheel Balance Cancer Therapy (WBCT). Methods The cases of 33 patients with advanced NSCLC who were treated with WBCT at the East West Cancer Center (EWCC) between October 4, 2004, and October 3, 2013, without undergoing concurrent conventional treatment were analyzed. The Kaplan-Meier method was used to estimate the OS of the cases, and the median OS was calculated according to age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), conventional-treatment history, WBCT treatment duration, and histological tumor type. Results The median OS of all patients was 31.1 (95% confidence interval [CI] = 3.5-58.7) months; the OS rates were 63.6% and 24.2% at years 1 and 2, respectively. The median OS rates of patients under and over 65 years were 45.2 (95% CI = 13.5-76.9) and 19.5 (95% CI = 7.1-31.8) months, respectively (P = .189). The median OS rates of patients who received WBCT for >14 days but treatment and those who had not were 45.2 (95% CI = 9.1-81.3) and 3.9 (95% CI = unable to calculate) months, respectively (P = .000). The median OS rates of patients with squamous cell carcinoma (SCC) and non-SCC lung cancer were 5.6 (95% CI = unable to calculate) and 45.2 (95% CI = 9.1-81.3) months, respectively (P = .262). The median OS rate of patients with ECOG PS ≥3 was 14.3 (95% CI = 8.8-19.8) months; that of patients ECOG PS treatment and have an ECOG PS <3.

  9. New targeted treatments for non-small-cell lung cancer – role of nivolumab

    Directory of Open Access Journals (Sweden)

    Zago G

    2016-08-01

    Full Text Available Giulia Zago,1,2,* Mirte Muller,1,* Michel van den Heuvel,1 Paul Baas1 1Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AvL, Amsterdam, the Netherlands; 2Medical Oncology 2, Istituto Oncologico Veneto (IOV, Padova, Italy *These authors contributed equally to this work Abstract: Non-small-cell lung cancer (NSCLC is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017 and non-squamous NSCLC (CheckMate 057. In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively. Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. Keywords: nivolumab, advanced non-small-cell lung cancer, immunotherapy, anti-PD-1

  10. Clinical potential of necitumumab in non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Genova C

    2016-08-01

    Full Text Available Carlo Genova,1–3 Fred R Hirsch1 1Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA; 2Lung Cancer Unit, IRCCS AOU San Martino IST, 3Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy Abstract: Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial; by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial. On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment. Keywords: necitumumab, EGFR, non-small cell lung cancer, monoclonal antibody, H-score

  11. A Clinical Study on Global TCM Therapy in Treating Senile Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To assess the clinical efficacy of global traditional Chinese medicine(TCM)therapy in treating senile advanced non-small cell lung cancer(NSCLC),with the aim of seeking a standardized,rational and economical way to treat advanced NSCLC in old patients.Methods:A retrospective analysis and comparison was carried out in 86 patients with senile advanced NSCLC,44 treated by global TCM(TCM group)and 42 by chemotherapy(control group)through dynamical observation on related indexes including tumor size,quality of life and the survival time,as well as on the fee for medical service at various time points in the course of the treatment.Results:The changes of tumor size,score of clinical main symptoms and behavior condition(by ZPS scoring),as well as survival rates in the two groups at corresponding time points,were not different significantly(P>0.05).The mean survival time in the TCM group was 13.20±1.52 months and that in the chemotherapy group was 13.45±1.94 months,showing insignificant difference between them.However,the median survival time in the TCM group(12 months)was actually longer than that in the chemotherapy group (9 months,P<0.05).The mean daily expense and the mean expense(RMB yuan)for each patient in the TCM group were significantly lower than that in the control group,which was 180.73±93.21 vs 825.84±329.63 for the mean daily expense and 34 077.21±14 638.04 vs 58 516.59±45 429.76 for the mean expense for each patient(both P<0.01).Conclusion:Treatment of senile advanced NSCLC with TCM alone has its apparent superiority in stabilizing tumor focus,improving clinical symptoms,elevating quality of life and prolonging the survival time.TCM is also less expensive,making it a good alternative therapeutic approach for this specific group of people.

  12. Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-sheng; MIAO Li-yun; LIU Lu; CAI Hou-rong; DING Jing-jing; REN Sheng-xiang; ZHOU Cai-cun

    2013-01-01

    Background Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients.This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.Methods A total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study.Blood samples were collected before the initiation of erlotinib treatment,and the levels of IL-1,IL-2R,IL-6,and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA).Cutoff points were defined as the median levels of IL-1 (low (≤26.5 pg/ml) and high (>26.5 pg/ml)),IL-2R (low (≤115 pmol/L) and high (>15 pmol/L)),IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)),and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ ml)).Kaplan-Meier analysis was used to estimate the survival time,and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes,including time to progression (TTP) and overall survival (OS).Results Between January 2007 and May 2011,162 patients were enrolled.Their median age was 58 years.In this group,109 were males and 53 were females,74 were former or current smokers and 88 were non-smokers.A total of 122 patients had adenocarcinoma,27 had squamous cell carcinoma,and 13 had tumors with other types of histology.And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1,while 23 scored at 2-3.Expression of IL-1,IL-2R,and IL-6 was not significantly associated with age,gender,ECOG performance status,smoking status,or histology and stage of tumor.Only TNF-α was associated with smoking status (P=0.045).Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTp and OS than patients with high

  13. Erlotinib dosing-to-rash: A phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer

    NARCIS (Netherlands)

    A. mita (Alain); K. Papadopoulos (K.); M.J.A. de Jonge (Maja); G. Schwartz (G.); J. Verweij (Jaap); A. Ricart (A.); Q.S.C. Chu (Q. S C); A.W. Tolcher (A. W.); L. Wood (Lori); S.W. McCarthy (Stanley); M. Hamilton; K.K. Iwata (Kenneth); B. Wacker; K. de Witte (Karel); E.K. Rowinsky (Eric Keith)

    2011-01-01

    textabstractBackground: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacok

  14. Sunitinib Plus Erlotinib for the Treatment of Advanced/Metastatic Non-Small-Cell Lung Cancer A Lead-In Study

    NARCIS (Netherlands)

    Blumenschein, George R.; Ciuleanu, Tudor; Robert, Francisco; Groen, Harry J. M.; Usari, Tiziana; Ruiz-Garcia, Ana; Tye, Lesley; Chao, Richard C.; Juhasz, Erzsebet

    2012-01-01

    Background: This randomized, double-blind, multicenter study evaluated sunitinib plus erlotinib versus placebo plus erlotinib. Subjects with advanced non-small-cell lung cancer had received prior treatment with a platinum-based regimen. Here, we report safety, pharmacokinetics, and antitumor activit

  15. Randomized Phase II and Pharmacogenetic Study of Pemetrexed Compared With Pemetrexed Plus Carboplatin in Pretreated Patients With Advanced Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Smit, Egbert F.; Burgers, Sjaak A.; Biesma, Bonne; Eppinga, Pier; Dingemans, Anne-Marie C.; Joerger, Markus; Schellens, Jan H.; Vincent, Andrew; van Zandwijk, Nico; Groen, Harry J. M.

    2009-01-01

    Purpose We performed a randomized phase II trial comparing pemetrexed with pemetrexed plus carboplatin (PC) in patients experiencing relapse after platinum-based chemotherapy. Patients and Methods Main eligibility criteria were histologic or cytologic proof of advanced non-small-cell lung cancer (NS

  16. Retreatment with Epidermal Growth Factor Receptor Inhibitor After Initial Failure in Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Tongtong AN

    2011-03-01

    Full Text Available Background and objective The epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI shows favorable antitumor activity against chemorefractory non-small cell lung cancer (NSCLC. However, patients with advanced NSCLC have limited treatment options available if they are refractory to EGFR-TKI. To study the influence of the retreatment EGFR-TKI after failure of first-line TKI, we carried out this retrospective study. Methods Total 71 patients were analyzed who experienced treatment failure from their initial use of EGFR-TKI. After a period of time, they were retreated with TKI as tumor progression was observed. Results Of the 71 patients who received retreatment TKI, it was observed in 7% in partial response (PR, 36.6% in stable disease (SD, 56.3% in progressive disease (PD. Disease control rate (DCR was 43.7%. Twenty-six (36.6% patients were well controlled by retreatment with TKI monotherapy for not less than 3 months. Five (7.0% patients had partial response. Exon 21 mutation, PFS not less than 6 months during initial treatment TKI, and the interval not less than 3 months between initial treatment, and retreatment with TKI was associated with a good progression free survival based on univariate COX analysis (P=0.034; P=0.013; P=0.046. Conclusion It has been shown the possibility that retreatment with TKI might be useful when (1 Exon 21 has active mutation, (2 initial treatment shows a favorable PFS (≥ 6 months, and (3 there has been a period of time (≥3 months following the termination of the initial TKI treatment.

  17. 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.

  18. 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.

  19. Clinical retrospective analysis of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Platania, Marco; Agustoni, Francesco; Formisano, Barbara; Vitali, Milena; Ducceschi, Monika; Pietrantonio, Filippo; Zilembo, Nicoletta; Gelsomino, Francesco; Pusceddu, Sara; Buzzoni, Roberto

    2011-09-01

    In order to evaluate the clinical efficacy and the safety profile of molecularly targeted therapies as a palliative approach in elderly populations affected by advanced thoracic neoplasms, we retrospectively studied, in terms of effectiveness and toxicities, a group of pretreated elderly metastatic non-small cell lung cancer (NSCLC) patients admitted to our institution and treated with erlotinib at standard daily/dose. Forty-three patients aged 70 years or older who had previously failed on chemotherapy or radiotherapy were treated with oral Eerlotinib (150 mg/d) until disease progression or unacceptable toxicity. Clinical data, pathological types, potential prognostic factors, efficacy and toxicity of erlotinib were included in this analysis. In our series we observed: objective responses in six patients (14%) and stable disease in 15 (35%). Skin rash was the most common side effect (67%). Grade 3-4 adverse events were observed in 16 cases (37%). The median overall survival and the median progression-free survival were 8.4 months (CI 95%: 0.7-43.6) and 3 months (CI 95%: 0.4-28.4), respectively. Patients with adenocarcinoma achieved the best disease control rate (p = 0.027), while not/former smokers showed a better response (p = 0.069). In our experience the use of erlotinib after chemotherapy failure in an unselected elderly population affected by NSCLC showed moderate efficacy and a moderate safety profile. However, erlotinib represents a valid option in this setting, but other factors such as biological information, comorbidities and concomitant medications need to be carefully take into consideration in this particular subset of cancer patients.

  20. Toxicity of concurrent radiochemotherapy for locally advanced non--small-cell lung cancer: a systematic review of the literature.

    Science.gov (United States)

    Koning, Caro C; Wouterse, Sanne J; Daams, Joost G; Uitterhoeve, Lon L; van den Heuvel, Michel M; Belderbos, José S

    2013-09-01

    Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two meta-analyses were inconclusive in an attempt to define the optimal concurrent RCT scheme. Besides efficacy, treatment toxicity will influence the appointed treatment of choice. A systematic review of the literature was performed to record the early and late toxicities, as well as overall survival, of concurrent RCT regimens in patients with NSCLC. The databases of PubMed, Ovid, Medline, and the Cochrane Library were searched for articles on concurrent RCT published between January 1992 and December 2009. Publications of phase II and phase III trials with ≥ 50 patients per treatment arm were selected. Patient characteristics, chemotherapy regimen (mono- or polychemotherapy, high or low dose) and radiotherapy scheme, acute and late toxicity, and overall survival data were compared. Seventeen articles were selected: 12 studies with cisplatin-containing regimens and 5 studies using carboplatin. A total of 13 series with mono- or polychemotherapy schedules--as single dose or double or triple high-dose or daily cisplatin-containing (≤ 30 mg/m(2)/wk) chemotherapy were found. Acute esophagitis ≥ grade 3 was observed in up to 18% of the patients. High-dose cisplatin regimens resulted in more frequent and severe hematologic toxicity, nausea, and vomiting than did other schemes. The toxicity profile was more favorable in low-dose chemotherapy schedules. From phase II and III trials published between 1992 and 2010, it can be concluded that concurrent RCT with monochemotherapy consisting of daily cisplatin results in favorable acute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets.

  1. 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.

  2. Efficacy and clinical/molecular predictors of erlotinib monotherapy for Chinese advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHU Yu-jia; XIA Ying; REN Guan-jun; WANG Meng-zhao; ZENG Xuan; ZHANG Li

    2010-01-01

    Background A retrospective analysis of clinical data were conducted reviewing patients who were given erlotinib at Peking Union Medical College (PUMC) Hospital from May 2005 to December 2009. Relationships between clinical factors, epidermal growth factor receptor (EGFR) mRNA expression, EGFR gene mutations, KRAS gene mutations and clinical outcomes were investigated in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods Patients with stage ⅢB/Ⅳ NSCLC who had not previously participated in erlotinib related clinical trials were enrolled into this study. All patients were given oral erlotinib 150 mg per day. Tumor samples of some patients were accessed with mutant-enriched polymerase chain reaction assay (EGFR, KRAS gene mutations) and multiplex branched DNA assay (EGFR mRNA expression).Results Seventy-nine patients were enrolled in this study, 23 patients had a partial response (PR), 36 patients had a stable disease (SD), 20 patients had a PD, with an objective response rate of 29.1%, and a disease control rate of 74.7%.Females (P=0.023), non-smokers (P=0.013), patients with a skin rash (P=0.047), and with highly differentiated tumors (P=0.037) were significantly correlated with the objective response rate. Patients with a lower ECOG PS (P=0.002),highly differentiated tumors (P=0.014), non-smokers (P=0.002), and patients with a skin rash (P <0.001) were significantly correlated with the disease control rate. The median progression-free survival was 35 weeks (95% CI: 13-57 weeks) and 1-year survival was 72.3%. Highly-differentiated tumors (P=0.027) and patients with a skin rash (P <0.001)were significantly correlated with PFS. Seventeen patients were tested for EGFR/KRAS gene mutations and EGFR mRNA expression. Progression-free survival (PFS) of patients with EGFR exon 19/21 mutations was 66 weeks, longer than patients with wild type EGFR exon 19/21 (P=0.018). No significant relationships were found between EGFR mRNA expression, EGFR

  3. Concurrent Chemoradiotherapy with Biweekly Gemcitabine and Cisplatin in Patients with Locally Advanced Non-small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oak, Chul Ho; Kim, Ja Kyung; Jang, Lee La; Moon, Dae Sung; Jang, Tae Won; Jung, Maan Hong; Cho, Sung Whan; Jeung, Tae Sig [Kosin University College of Medicine, Busan (Korea, Republic of)

    2008-09-15

    In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy (CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine (500 mg/m2) and cisplatin (30 mg/m2) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine (1,200 mg/m2, 1st and 8th day) and cisplatin (60 mg/m2) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range 3-39 months) and the median survival time was 16 months (95% CI; 2.4-39.2 months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine (500 mg/m2) and cisplatin

  4. Thermo-chemotherapy of GP or TP for Advanced Non-small Cell Lung Cancer: 
A Systematic Review

    Directory of Open Access Journals (Sweden)

    Denghai MI

    2012-08-01

    Full Text Available Background and objective Advanced non-small cell lung cancer (NSCLC is characterized by poor treatment efficacy and short survival time. Clinical trials have shown that the combination of chemotherapy with thermotherapy exhibits strong efficacy. We performed this meta-analysis to evaluate the clinical efficacy and safety of gemcitabine plus cisplatin (GP and paclitaxel plus cisplatin (TP combined with thermotherapy in the treatment of NSCLC, as well as to provide reference for clinical practice and future research. Methods We searched international (Cochrane Library, PubMed, and EMBASE and Chinese (CBM, CNKI, VIP and Wanfang databases for relevant articles and imported other retrievable sources, such as tracing-related references. We also corresponded with other authors to obtain certain inaccessible information. Data from all relevant randomized controlled trials (RCT were collected to compare GP or TP thermochemotherapy with GP or TP chemotherapy alone. The quality of the included studies was assessed by adequate outcome-based standards and clinical circumstances. The meta-analysis was conducted using RevMan 5.1. Results Fifteen RCTs involving 952 patients were included in this meta-analysis. The results showed that the thermochemotherapy group had higher rates of improvement in quality of life (OR=3.84, 95%CI: 2.61-5.64, survival at 1 year (HR=1.94, 95%CI: 1.21-3.12, and survival at 2 years (HR=2.05, 95%CI: 1.18-3.58 compared with the chemotherapy group, with the differences between them being significant. However, these groups did not differ in other indicators of treatment effectiveness, such as myelosuppression, alimentary canal reactions, hepatic lesions, and diarrhea. Conclusion Compared with chemotherapy alone, thermochemotherapy can improve survival rates and curative effects, ameliorate symptoms, and enhance the quality of life of patients with advanced NSCLC, and it has an acceptable safety profile. The results of this meta

  5. Effect of integrated Chinese medical treatment on the survival time of patients with advanced non-small-cell lung cancer: a clinical study

    Institute of Scientific and Technical Information of China (English)

    刘苓霜

    2014-01-01

    Objective To observe clinical effect of integrated Chinese medical(CM)treatment(as maintenance therapy)on the progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small-cell lung cancer(NSCLC)after first-line chemotherapy.Methods The study was a prospective,randomized,controlled clinical trial.Totally 69 non-progressive advanced NSCLC patients treated with first-line chemotherapy were

  6. Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

    Science.gov (United States)

    Takigawa, N; Kiura, K; Segawa, Y; Watanabe, Y; Kamei, H; Moritaka, T; Shibayama, T; Ueoka, H; Gemba, K; Yonei, T; Tabata, M; Shinkai, T; Hiraki, S; Takemoto, M; Kanazawa, S; Matsuo, K; Tanimoto, M

    2006-01-01

    Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0–4.9). PMID:17031394

  7. Effectiveness of third-generation chemotherapy on the survival of patients with advanced non-small cell lung cancer in Norway

    DEFF Research Database (Denmark)

    von Plessen, C; Strand, T-E; Wentzel-Larsen, T;

    2008-01-01

    BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation of chemo......BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation...... of death (HR 0.84, 95% CI 0.73 to 0.98). County of residence predicted chemotherapy utilisation with odds ratios in the range 0.13 (95% CI 0.1 to 0.19) to 1.04 (95% CI 0.64 to 1.69), a county with traditionally high utilisation as reference. CONCLUSION: Utilisation of third-generation chemotherapy...

  8. Advances in the Molecular Mechanisms and Prognostic Significance of EMT 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Qinchen CAO

    2014-07-01

    Full Text Available Epithelial to mesenchymal transition (EMT has an important role in the development of embryo, as well as that in the metastasis of non-small cell lung cancer (NSCLC. Recent researches have demonstrated that both morphological and phenotypic conversions emerge in cells undergoing EMT. As most of relevant studies were on other cancers, it is essential to uncover whether it is the similar mechanisms accounting for EMT in NSCLC. With the progress of the studies, EMT-related basic researches are gradually applied to predicting the prognosis of NSCLC. The aim of this article was to discuss the mechanisms related to EMT emerging in NSCLC.

  9. Chronic myelomonocytic leukemia blast crisis in a patient with advanced non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors.

    Science.gov (United States)

    Ogata, Hiroaki; Okamoto, Isamu; Yoshimoto, Goichi; Obara, Teppei; Ijichi, Kayo; Iwama, Eiji; Harada, Taishi; Akashi, Koichi; Nakanishi, Yoichi

    2017-03-01

    A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis. Physicians should be aware of such risks and monitor EGFR-TKI-treated patients with myeloid neoplasms accordingly.

  10. Advances in Liquid Biopsy and its Clinical Application in the Diagnosis 
and Treatment of Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Difan ZHENG

    2016-06-01

    Full Text Available With the advances of technology, great progresses have been made in liquid biopsy in recent years. Liquid biopsy is currently playing a more and more important role in early diagnosis and treatment of cancer. Compared with traditional tissue biopsy, liquid biopsy is more popular in clinical practice due to its non-invasiveness, convenience and high repeatability. It has huge potential in the future. This review introduces circulating tumor cells (CTCs and circulating tumor DNA (ctDNA as the most important objects in liquid biopsy, mainly focusing on their history, biological characteristics, detection technologies, limitations and applications in non-small cell lung cancer.

  11. 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.......039 and 10.9 vs. 14.3 months, p=0.038, respectively). IGF1R protein expression showed a similar, although non-significant tendency. CONCLUSION: IGF1R mRNA expression may be a prognostic biomarker in advanced NSCLC and should be investigated in a larger population....

  12. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yuan Y

    2014-05-01

    Full Text Available Ying Yuan, Xiao-Fen Li, Jia-Qi Chen, Cai-Xia Dong, Shan-Shan Weng, Jian-Jin HuangDepartment of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaAbstract: Past studies have demonstrated that epidermal growth factor receptor (EGFR tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC and sensitive EGFR gene mutations. Gefitinib (Iressa®, the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood–brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.Keywords: gefitinib, non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor

  13. Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

    Science.gov (United States)

    2016-08-25

    Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  14. 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.

  15. Circulating Thrombospondin-2 and FGF-2 in Patients with Advanced Non-small Cell Lung Cancer: Correlation with Survival.

    Science.gov (United States)

    Naumnik, W; Ossolińska, M; Płońska, I; Chyczewska, E; Nikliński, J

    2015-01-01

    Thrombospondin-2 (TSP-2) is an endogenous negative regulator of vascularization in human cancer. TSP-2 regulates angiogenesis through binding and sequestration of the proangiogenic fibroblast growth factor-2 (FGF-2). However, it is unclear whether TSP-2 and FGF-2 are related to prognosis in non-small cell lung cancer (NSCLC). To study this issue, we measured serum (Elisa) levels of TSP-2 and FGF-2 in 40 NSCLC patients (before chemotherapy) and 22 healthy subjects. Both TSP-2 and FGF-2 concentrations were elevated in the NSCLC group compared with control (TSP-2: 26.72±8.00 vs. 18.64±5.50 ng/ml, p=0.002; FGF-2: 11.90±5.80 vs. 7.26±3.90 pg/ml, p=0.01). Receiver-operating characteristic (ROC) curves were applied to find the cut-off serum levels of TSP-2 and FGF-2 (NSCLC vs. healthy: TSP-2=15.09 ng/ml, FGF-2=2.23 pg/ml). Patients before treatment with the TSP-2 level24.15 ng/ml had only 9 months' median survival (p=0.007). Patients with FGF-2 level>11.21 pg/ml had significantly shorter survival than patients with FGF-2FGF-2 than healthy people. High levels of TSP-2 and FGF-2 may predict worse survival.

  16. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer.

    Science.gov (United States)

    Yuan, Ying; Li, Xiao-Fen; Chen, Jia-Qi; Dong, Cai-Xia; Weng, Shan-Shan; Huang, Jian-Jin

    2014-01-01

    Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa(®)), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood-brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

  17. A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Kim, E S; Lu, C; Khuri, F R; Tonda, M; Glisson, B S; Liu, D; Jung, M; Hong, W K; Herbst, R S

    2001-12-01

    Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.

  18. 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

  19. 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

  20. Assessment of quality of life in patients with advanced non-small cell lung carcinoma treated with a combination of carboplatin and paclitaxel

    Directory of Open Access Journals (Sweden)

    Camila Uanne Resende Avelino

    2015-04-01

    Full Text Available OBJECTIVE: Non-small cell lung carcinoma (NSCLC is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. METHODS: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. RESULTS: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. CONCLUSIONS: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC.

  1. 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.

  2. 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

    Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study...... compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] cisplatin 75 mg/m(2) on day 1...... and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles. Results Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/ gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0...

  3. Genetic polymorphism in the epidermal growth factor receptor gene predicts outcome in advanced non-small cell lung cancer patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Nissen, Peter H.; Jakobsen, Kristine Raaby;

    2015-01-01

    OBJECTIVES: Epidermal growth factor receptor (EGFR) mutations are important predictors of treatment response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, some patients with mutations do not respond and some patients without mutations show...... with advanced NSCLC. Genotypes were correlated with clinical characteristics, toxicity and outcome. A multivariate analysis was performed using Cox proportional hazards model while adjusting for clinically relevant factors including EGFR mutation status. RESULTS: 181946CT or TT genotypes showed an association...... response. We therefore need additional biomarkers to improve the selection of these patients for treatment. A promising candidate could be germline genetic variations in the EGFR gene that can alter protein expression or function and may influence the response to TKIs. Thus, the aim of this study...

  4. Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Sundstrøm, Stein; Kaasa, Stein;

    2010-01-01

    AIM OF THE STUDY: To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other....... Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Toxicity was graded using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30...... neutropenic fevers (12% versus 5%; p=.012) and deaths from neutropenic infections (3% versus 0%; p=.027). They had more thrombocytopenia (46% versus 36%; p=.03), but not more thrombocytopenic bleedings (3% versus 4%; p=.65). In general, the patients with severe comorbidity reported poorer HRQoL...

  5. Usefulness of circulating free DNA for monitoring epidermal growth factor receptor mutations in advanced non-small cell lung cancer patients: a case report

    Science.gov (United States)

    Gonzalez-Cao, Maria; Ramirez, Santiago Viteri; Ariza, Nuria Jordana; Balada, Ariadna; Garzón, Mónica; Teixidó, Cristina; Karachaliou, Niki; Morales-Espinosa, Daniela; Molina-Vila, Miguel Ángel; Rosell, Rafael

    2016-01-01

    Genomic analysis of circulating tumor DNA (ctDNA) released from cancer cells into the bloodstream has been proposed as a useful method to capture dynamic changes during the course of the disease. In particular, the ability to monitor epidermal growth factor receptor (EGFR) mutation status in cell-free circulating DNA (cfDNA) isolated from advanced non-small cell lung cancer (NSCLC) patients EGFR can help to the correct management of the disease and overcome the challenges associated with tumor heterogeneity and insufficient biopsied material to perform key molecular diagnosis. Here, we report a case of long term monitorization of EGFR mutation status in cfDNA from peripheral blood in an NSCLC patient in, with excellent correlation with clinical evolution. PMID:27826535

  6. Long-term Survival of A Patient with Advanced Non-small Cell Lung Cancer 
on Bevacizumab Therapy: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Wei WU

    2013-06-01

    Full Text Available We report an advanced stage Chinese female lung adenocarcinoma patient who was negative for epidermal growth factor receptor (EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS gene mutations, also negative for chinodem microtubule-associated protein-like 4/anaplastic lymphoma kinase (EML4-ALK gene rearrangement and treated with bevacizumab (15 mg/kg in combination with 6 cycles of conventional doses of paclitaxel and carboplatin chemotherapy. She was then treated with maintenance bevacizumab for a total of 42 cycles, the total dose of bevacizumab is 44,730 mg. The progression-free survival was 39 months. Our findings suggest that maintenance bevacizumab for the treatment of non-small cell lung cancer (NSCLC is safe and its benefit for long-term survival overwhelms its side effects.

  7. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas Hg

    2011-06-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician's discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account.

  8. 晚期非小细胞肺癌的治疗选择%Recent progress on the treatment of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘潇衍; 李峻岭

    2015-01-01

    Lung cancer is the leading cause of cancer death worldwide. Significant advancements have been observed in the thera-py for non-small cell lung cancer (NSCLC). With constant extension of new awareness regarding the histopathology of lung cancer, ho-mologous chemotherapeutic regimens have been developed on the basis of histopathological sub-typing methods. With developments in molecular biology, driving gene mutations during tumorigenesis and progression have been discovered. A series of targeted drugs for various molecular subtypes has also been investigated and developed on the basis of these mutations. This review summarizes recently published clinical outcomes on the management of advanced NSCLC and strategies to apply drugs in clinical treatments.%肺癌是世界范围内癌症相关死亡的首要病因.近年来,非小细胞肺癌(non-small cell lung cancer,NSCLC)的治疗取得了巨大进步.人们对肺癌病理组织学认识不断深入,根据病理组织分型制订了相应的化疗方案.此外随着对分子生物学研究的发展,人们发现了在肿瘤发生发展过程中的驱动性基因突变,并以此研发了一系列针对不同分子亚型的靶向药物.本文将结合近期一系列临床研究结果,对晚期NSCLC的临床治疗策略进行论述.

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

    Directory of Open Access Journals (Sweden)

    Bearz Alessandra

    2008-07-01

    Full Text Available Abstract Background The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC. Methods Overall, 95 patients received pemetrexed 500 mg/m2 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. Results 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. Conclusion Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.

  10. Genetic variants of CHRNA5-A3 and CHRNB3-A6 predict survival of patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Wang, Yang; Peng, Xiaonu; Zhu, Lijun; Hu, Likuan; Song, Yipeng

    2016-05-03

    Nicotinic acetylcholine receptors (nAChRs) play a key role in carcinogenesis and progression of lung cancer; and polymorphisms in CHRNA5-A3 and CHRNB3-A6, two gene clusters encoding nAChR subunits, have been associated with lung cancer risk. In this study, we investigated whether variants in the two gene clusters were associated with prognosis of advanced non-small cell lung cancer (NSCLC). A total of 165 stage IIIB-IV NSCLC patients were enrolled in this study. Three polymorphisms (rs667282 and rs3743073 in CHRNA5-A3 and rs13280604 in CHRNB3-A6) were genotyped using the TaqMan method. Overall survival (OS) was estimated using the log-rank test and the Cox models. Our results showed that patients with CHRNA5-A3 rs667282 TT or TC genotypes had a significantly shorter OS than those carrying the CC genotype (Log-rank, P = 0.043). Furthermore, multivariate Cox regression analysis showed that rs667282 TT/TC genotypes are significantly associated with increased risk of overall deaths (adjusted hazard ratio, 1.7; 95% CI, 1.1-2.7). However, the similar results were not observed for other two polymorphisms. Furthermore, no evident association was found between these variants and clinicopathologic features of advanced NSCLC. Our present study suggested that rs667282 in CHRNA5-A3 may modify the prognosis of patients with advanced NSCLC.

  11. The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer.

    Science.gov (United States)

    Lee, Dong-Soo; Kim, Yeon-Sil; Jung, So-Lyoung; Lee, Kyo-Young; Kang, Jin-Hyoung; Park, Sarah; Kim, Young-Kyoon; Yoo, Ie-Ryung; Choi, Byung-Ock; Jang, Hong-Seok; Yoon, Sei-Chul

    2012-08-01

    Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

  12. Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

    Institute of Scientific and Technical Information of China (English)

    Jin-ji Yang; Qing Zhou; Ri-qiang Liao; Yi-sheng Huang; Chong-rui Xu; Zhen Wang; Bin-chao Wang; Hua-jun Chen; Yi-long Wu

    2012-01-01

    Objective:To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non-small cell lung cancer (NSCLC).Methods:Sixty-two patients with previously untreated advanced NSCIC were recruited between June 2006 and November 2007.Subjects were randomly assigned to the NG arm (n=30) and the CG arm (n=32).Only patients (24 and 25 in the NG and CG arms,respectively) who completed ≥2 chemotherapy cycles were included in the data analysis.The primary outcome measure was the objective response rate (ORR).The secondary outcome measures included progression-free survival (PFS),overall survival (OS) and adverse events.Results:There were no statistically significant differences in the efficacy measures (ORR,P=0.305; median PFS,P=0.198; median OS,P=0.961) or in the major adverse events (grade 3/4 neutropenia,P=0.666; grade 3/4 anemia,P=0.263; grade 3/4 thrombocytopenia,P=0.212) between the two treatment arms.However,there was a trend towards higher ORR (37.5% vs.24.0%),longer PFS (6.0 vs.5.0 months),and less adverse events in the NG arm.Conclusion:NG regimen seems to be superior over CG regimen for advance NSCLS,but further investigation is needed to validate this superiority.

  13. Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data.

    Science.gov (United States)

    Reboul, François L

    2004-02-01

    Over the past 20 years, combined treatment with radiotherapy and second-generation chemotherapy drugs was extensively studied in patients with locally advanced NSCLC and became the standard over radiotherapy alone in patients with good performance status. Radiosensitizing properties of cisplatin have been identified in the laboratory. Close temporal administration of cisplatin and radiation is mandatory for enhanced antitumor efficacy, but results in significant toxicity to normal tissues. Early clinical studies demonstrated that the concurrent administration of cisplatin during STD-RT was feasible, with acceptable esophageal toxicity, and had the potential of significantly improving locoregional control. Carboplatin administered concurrently with accelerated HFX-RT was responsible for a higher rate of esophageal toxicity. Further improvement in survival also requires an effective treatment of micro-metastatic disease through full-dose delivery of cytotoxic drugs and the addition of at least one more active drug in conjunction with cisplatin and radiotherapy to further improve locoregional control of the disease. In most clinical studies, etoposide was the second drug of choice because of its own radiosensitizing properties and possible synergy with cisplatin. In numerous phase II studies, concurrent radiotherapy and PE resulted in reproducible results in terms of local control (30%-40%), median survival (15-18 months), survival at 2 years (35%-40%), and survival at 5 years (25%-30%). In phase III studies, these results were shown to be superior to radiotherapy alone and to induction chemotherapy followed by STD-RT. The question of the potential benefit of HFX-RT combined with PE has been addressed in phase II and III studies. At this time, there is no firm evidence that concurrent chemotherapy with HFX-RT is superior to concurrent chemotherapy with STD-RT in terms of local control and survival. Only a significant benefit in terms of local control or survival would

  14. The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer?

    Science.gov (United States)

    2017-01-01

    Specific mutations in epidermal growth factor receptor (EGFR) gene are predictive for response to the EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer patients (NSCLC). According to international guidelines, the molecular testing in patients with advanced NSCLC of a non-squamous subtype is recommended. However, obtain a tissue sample could be challenging. Liquid biopsy allows to determine patients suitable for EGFR-targeted therapy by analysis of circulating-free tumor DNA (cfDNA) in peripheral blood samples and might replace tissue biopsy. It allows to acquire a material in convenient minimally invasive manner, is easily repeatable, could be used for molecular identification and molecular changes monitoring. Many studies show a high concordance rate between tissue and plasma samples testing. When U.S. Food and Drug Administration (FDA) approved the first liquid biopsy test, analysis of driver gene mutation from cfDNA becomes a reality in clinical practice for patients with NSCLC.

  15. 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

  16. 125I brachytherapy of locally advanced non-small-cell lung cancer after one cycle of first-line chemotherapy:a comparison with best supportive care

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    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

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

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    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.

  18. A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer.

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    Chikamori, Kenichi; Kishino, Daizo; Takigawa, Nagio; Hotta, Katsuyuki; Nogami, Naoyuki; Kamei, Haruhito; Kuyama, Shoichi; Gemba, Kenichi; Takemoto, Mitsuhiro; Kanazawa, Susumu; Ueoka, Hiroshi; Segawa, Yoshihiko; Takata, Saburo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune

    2009-07-01

    A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

  19. A phase I study of S-1 with concurrent thoracic radiotherapy in elderly patients with localized advanced non-small cell lung cancer.

    Science.gov (United States)

    Takigawa, Nagio; Kiura, Katsuyuki; Hotta, Katsuyuki; Hosokawa, Shinobu; Nogami, Naoyuki; Aoe, Keisuke; Gemba, Kenichi; Fujiwara, Keiichi; Harita, Shingo; Takemoto, Mitsuhiro; Himei, Kengo; Shinkai, Tetsu; Fujiwara, Yoshirou; Takata, Saburo; Tabata, Masahiro; Kanazawa, Susumu; Tanimoto, Mitsune

    2011-01-01

    S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.

  20. Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR-mutated non-small cell lung cancer treated with erlotinib

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Demuth, Christina; Weber, Britta;

    2016-01-01

    OBJECTIVES: The central immune co-inhibitory programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway plays a key role in tumor immune evasion in non-small cell lung cancer (NSCLC). Soluble PD-1 (sPD-1) can be detected in the blood, and preclinical evidence suggests that sPD-1 blocks PD-1/-L1...... interaction and improves anti-tumor immunity. The present study compares the concentration of sPD-1 in the serum of advanced NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutation prior to erlotinib treatment and at the time of progression and correlates these results to patient outcome....... MATERIALS AND METHODS: Blood samples from 38 patients with EGFR-mutated advanced NSCLC treated with erlotinib were analyzed for sPD-1 by sandwich ELISA. EGFR mutational status was assessed in circulating tumor DNA (ctDNA) and tumor biopsies. RESULTS: sPD-1 could be detected in 21% of patients prior...

  1. The Relationship between EGFR Mutations and Response and Prognosis of Tyrosine Kinase Inhibitors in Advanced Non-small-cell Lung Cancer

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    Xuebing LI

    2008-04-01

    Full Text Available Background and objectives It has been proven that epigermal growth factor receptor (EGFR signal pathway plaied an important role in the oncogenesis and development of non-small cell lung cancer (NSCLC. EGFR tyrosine kinase inhibitors (EGFR-TKIs are currently investigated in the treatment of NSCLC. It was suggested in previous studies that the EGFR gene mutations were correlated with the response to EGFR-TKIs therapy and prognosis of NSCLC. We studied the role of EGFR gene mutations in response to two kinds of TKIs therapy and prognosis of NSCLC in this study. Methods The tissue samples of 59 advanced NSCLC patients (34 patients receiving Gefitinib monotherapy and 25 patients receiving Erlotinib monotherapy were collected, and patient charts were reviewed. The mutations in exons 19 and 21 of EGFR gene were detected by PCR-PAGE and PCR-RFLP respectively. The sequences of interested fragments were verified by direct sequencing. Relationship between EGFR mutation and response to TKIs therapy was analyzed with X^2 test. Results EGFR gene mutations were identified in 22 of 59 samples (37.3%. EGFR gene mutation rate was significantly higher in female, non-smoker and patients with adenocarcinoma than in others (50% vs 18.9%, P0.05. Conclusions EGFR gene mutation occurs more frequently in female, non-smoker and patients with adenocarcinoma. In patients with advanced NSCLC, EGFR mutation is associated with good response to EGFR-TKIs therapy.

  2. Shenqi fuzheng, an injection concocted from chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review

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    Wang Min-Yan

    2010-10-01

    Full Text Available Abstract Background Platinum-based chemotherapy has been a standard therapy for advanced non-small cell lung cancer (NSCLC, but it has high toxicity. In China, Shenqi Fuzheng, a newly developed injection concocted from Chinese medicinal herbs has been reported that may increase efficacy and reduce toxicity when combined with platinum-based chemotherapy, but little is known about it outside of China. The aim of this study was to systematically review the existing clinical evidence on Shenqi Fuzheng Injection(SFI combined with platinum-based chemotherapy for advanced NSCLC. Methods Pubmed, Cochrane Library, EMBASE, CNKI, and CBM search were organized for all documents published, in English and Chinese, until April 2010. The randomized controlled clinical trials were selected based on specific criteria, in which a SFI plus platinum-based chemotherapy treatment group was compared with a platinum-based chemotherapy control group for patients with advanced NSCLC. The quality of studies was assessed by modified Jadad's scale, and Revman 4.2 software was used for data syntheses and analyses. Results Twenty nine studies were included in this review based on our selection criteria. Of them, ten studies were of high quality and the rest were of low quality, according to the modified Jadad scale. The meta-analysis showed there was a statistically significant higher tumor response (RR, 1.19; 95% CI, 1.07 to 1.32; P = 0.001 and performance status ((RR, 1.57; 95% CI, 1.45 to 1.70; P P = 0.016. Conclusions SFI intervention appears to be useful to increase efficacy and reduce toxicity when combined with platinum-based chemotherapy for advanced NSCLC, although this result needs to be further verified by more high-quality trials.

  3. Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHUO Ming-lei; DUAN Jian-chun; WANG Yu-yan; GUO Qing-zhi; LIU Xu-yi; LIU Ning-hong; WANG Jie; WU Mei-na; ZHAO Jun; Sonya Wei Song; BAI Hua; WANG Shu-hang; YANG Lu; AN Tong-tong; WANG Xin

    2011-01-01

    Background The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy,but its role in cytotoxic chemotherapy is still unknown.Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy.Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC).In this study,we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.Methods We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department.We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.Results There were 54 patients with known EGFR mutations and 91 cases of wild types.No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs.31.9%).The median survival time and 1-,2-year survival rates were higher in mutation carriers than wild-types (24months vs.18 months,85.7% vs.65.7% and 43.7% vs.25.9%,P=0.047).Clinical stage (IV vs.Ⅲb),response to the first-line chemotherapy (partial vs.no) and EGFR genotype were independent prognostic factors.Conclusion Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy,but an independent prognostic factor indicating longer survival.

  4. The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Wen-Feng Fang; Yu-Xiang Ma; Li Zhang; Yuan-Yuan Zhao; Ying Guo; Cong Xue; Zhi-Huang Hu; Yan Huang; Hong-Yun Zhao; Jing Zhang; Xuan Wu

    2014-01-01

    Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials-involving 11,456 adult patients in 32 arms-were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797,P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936,P < 0.001) but was not statisticaly significant in the trials in predominantly Caucasian populations (r = 0.116,P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.

  5. Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Isla D

    2016-12-01

    Full Text Available Dolores Isla,1 Javier De Castro,2 Oscar Juan,3 Santiago Grau,4 Javier Orofino,5 Rocío Gordo,5 Carlos Rubio-Terrés,6 Darío Rubio-Rodríguez6 1Medical Oncology Department, Clinical Universitary Hospital Lozano Blesa, Zaragoza, 2Medical Oncology Department, Universitary Hospital La Paz, Madrid, 3Medical Oncology Department, Universitary and Polytechnic Hospital La Fe, Valencia, 4Pharmacy Department, Del Mar Hospital, Barcelona, 5Roche Farma, S.A., Health Economics, 6Health Value, Health Economics, Madrid, Spain Objectives: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs are an established treatment for advanced non-small cell lung cancer (NSCLC with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR–TKI-related adverse events (AEs was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS.Methods: The frequency of AEs was established from a recently published meta-analysis. In Spain, the daily cost of both drugs can be considered similar; as a result, only the costs of management of the AEs were considered. Costs and resource utilization in the management of the AEs were estimated by a panel of Spanish oncologists and from studies previously carried out in Spain. A probabilistic analysis was performed based on a Monte Carlo simulation.Results: The model generated 1,000 simulations. The total cost per patient treated with erlotinib and afatinib was €657.44 and €1,272.15, respectively. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €550.86 and €106.58, respectively, whereas the cost with afatinib was €980.63 and €291.52, respectively. The reduction in the number of AEs with erlotinib could avoid a mean cost for the NHS of €614.71 (95% CI:

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

    Directory of Open Access Journals (Sweden)

    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

  7. Minimally invasive (robotic assisted thoracic surgery and video-assisted thoracic surgery) lobectomy for the treatment of locally advanced non-small cell lung cancer

    Science.gov (United States)

    Yang, Hao-Xian; Woo, Kaitlin M.; Sima, Camelia S.

    2016-01-01

    Background Insufficient data exist on the results of minimally invasive surgery (MIS) for locally advanced non-small cell lung cancer (NSCLC) traditionally approached by thoracotomy. The use of telerobotic surgical systems may allow for greater utilization of MIS approaches to locally advanced disease. We will review the existing literature on MIS for locally advanced disease and briefly report on the results of a recent study conducted at our institution. Methods We performed a retrospective review of a prospective single institution database to identify patients with clinical stage II and IIIA NSCLC who underwent lobectomy following induction chemotherapy. The patients were classified into two groups (MIS and thoracotomy) and were compared for differences in outcomes and survival. Results From January 2002 to December 2013, 428 patients {397 thoracotomy, 31 MIS [17 robotic and 14 video-assisted thoracic surgery (VATS)]} underwent induction chemotherapy followed by lobectomy. The conversion rate in the MIS group was 26% (8/31) The R0 resection rate was similar between the groups (97% for MIS vs. 94% for thoracotomy; P=0.71), as was postoperative morbidity (32% for MIS vs. 33% for thoracotomy; P=0.99). The median length of hospital stay was shorter in the MIS group (4 vs. 5 days; P<0.001). The 3-year overall survival (OS) was 48.3% in the MIS group and 56.6% in the thoracotomy group (P=0.84); the corresponding 3-year DFS were 49.0% and 42.1% (P=0.19). Conclusions In appropriately selected patients with NSCLC, MIS approaches to lobectomy following induction therapy are feasible and associated with similar disease-free and OS to those following thoracotomy. PMID:27195138

  8. Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data.

    Directory of Open Access Journals (Sweden)

    Wei-Xiang Qi

    Full Text Available BACKGROUND: Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC, but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC. METHODS: Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS, progression-free survival (PFS, overall response rate (ORR and grade 3 or 4 adverse event (AEs. The pooled hazard ratio (HR or odds ratio (OR, and 95% confidence intervals (CI were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95% CI: 0.82-0.99, p = 0.024, PFS (HR 0.83, 95% CI: 0.72-0.97, p = 0.018, and ORR (OR 1.35, 95% CI 1.01-1.80, P = 0.04. Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy. CONCLUSIONS: With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy.

  9. Translational Research on Epidermal Growth Factor Receptor Gene Mutations in Targeted Therapy for Patients with Advanced Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-yan; ZHOU Er-xi

    2015-01-01

    Objective:To explore the significance of epidermal growth factor receptor (EGFR) gene mutations in targeted therapy for patients with advanced non-small cell lung cancer (NSCLC). Methods:One hundred and seventeen patients with advanced NSCLC admitted in Maternal and Child Health Care Center of Zibo City from Jan., 2011 to Jan., 2014 were performed with EGFR gene detection and then divided into 3 groups according to the detecting results. Patients in group A and group B were given oral geiftinib, 250 mg/d while patients in Group C with docetaxel, 75 mg/m2. Chemotherapy for 3 groups was discontinued until severe adverse reactions or disease progression occurred, or continuous treatment was considered to be unfavorable by the doctors, or patients asked for withdrawal from the study. The relationship between clinicopathological features and EGFR mutations were analyzed. The short-term and long-term efifcacy and adverse reactions of 3 groups were observed. Results:Of the 31 cases with EGFR mutations, there were 16 cases (51.6%) of mutations in exon 19, 14 (45.2%) in exon 21 and 2 (6.45%) in exon 18. No EGFR mutation was found in exon 20. EGFR mutations were associated with histological types of tumors and whether patients were smoking. The median follow-up time was 26 months and 62 patients were dead. None of CR was in 3 groups. The disease control rate (DCR) in group A was obviously higher than that in group B (χ2=9.382,P=0.002), which was also higher in group C than that in group B (χ2=4.674,P=0.031). The 1-year survival rate in group A was obviously higher than that in group B and group C (P Conclusion:EGFR mutations are the main indicators for guiding the targeted therapy for patients with advanced NSCLC.

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

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    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.

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

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    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.

  12. Detection and Evaluation of EGFR Mutation Status in Serum of Patients with Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs

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    Ling MA

    2013-06-01

    Full Text Available Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs has shown a high response rate in the treatment of lung cancer in patients with (EGFR mutation. The aim of this study is to evaluate the relationship between EGFR mutation status in serum and predicting benefit from EGFR-TKIs therapy in patients with advanced non-small cell lung cancer (NSCLC. Methods We examined EGFR mutation status in serum of 80 patients with advanced, EGFR-TKIs given as first-line therapy NSCLC. All patients were received long-term follow-up, and the drug efficacy were observed and evaluated. Results The EGFR mutation in serum was detected in 33.8% (27/80 of NSCLC patients examined, in which exon 19 deletion mutation was present at a frequency of 44.4% (12/27 and exon 21 point mutation was 55.6% (15/27; The response rate to EGFR-TKI in patients with EGFR mutation in serum was (55.6%, 15/27, which was remarkably higher than that in EGFR wild-type patients (17.0%, 9/53, the difference was statistically significant (χ2=0.370, P<0.001; The median progression free survival (PFS of patients with EGFR mutation in serum was remarkably better than that of EGFR wild-type patients (9.8 months vs 5.7 months, P=0.014. Conclusion In patients with advanced, EGFR-positive in serum NSCLC, EGFR-TKIs given as first-line therapy is associated with improved drug efficacy. The results suggest that it is feasible to use serum to detect EGFR mutation, which can predict a benefit from EGFR-TKIs given as first-line therapy.

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

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    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.

  14. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: effects on quality of life and survival.

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    Guo, Li; Bai, Shu-Ping; Zhao, Ling; Wang, Xiao-Hong

    2012-09-01

    A platinum-based two-drug regimen is currently the standard of care for patients with advanced non-small-cell lung cancer (NSCLC). However, chemotherapy-induced side effects still remain a significant clinical problem. Astragalus polysaccharide (APS) is a polysaccharide isolated from the radix of astragalus membranaceus, a commonly used herbal compound in traditional Chinese medicine. APS was reported to increase tumor response, stabilize and improve performance status, and reduce chemotherapy toxicity. We designed this trial to determine whether APS injection integrated with vinorelbine and cisplatin (VC) offered an improved QOL over VC for patients with advanced NSCLC. Secondary objectives were tumor response, toxicity, and survival results. One hundred thirty-six patients with histologically or cytologically confirmed NSCLC were enrolled in this study from May 2008 to March 2010. Patients were randomized to receive either VC (VC arm) or VC combined with APS (VC-APS arm). The objective response rate of was 42.64% in the VC-APS arm and 36.76% in the VC arm. The difference was not statistically significant (P = 0.483). Median survival time was 10.7 and 10.2 months (P = 0.76) in VC-APS arm and VC arm, with 1-year survival rates of 35.3 and 32.4% (P = 0.717), respectively. After 3 cycles of treatment, there were significant differences in the overall patient QOL (P = 0.003), physical function (P = 0.01), fatigue (P pain (P = 0.007), and loss of appetite (P = 0.023) between the two study groups. In summary, we have proved that the treatment of APS integrated with VC had significantly improved QOL in patients with advanced NSCLC compared with VC alone.

  15. Targeted therapy for localized non-small-cell lung cancer: a review

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    Paleiron N

    2016-07-01

    Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

  16. Severe Organizing Pneumonia after Two Cycles of Docetaxel as Fourth-Line Chemotherapy for Advanced Non-Small Cell Carcinoma of the Lung

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    Jens Hasskarl

    2009-02-01

    Full Text Available Organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia, BOOP is an inflammatory process of the bronchioles that can lead to the destruction of small airways and surrounding lung tissue. Although the majority of cases are idiopathic, certain chemicals and drugs can induce OP. Here, we report a 54-year-old male patient with advanced non-small cell lung cancer (NSCLC who developed therapy-associated OP. He had undergone several other chemotherapies before being switched to docetaxel as monotherapy (75 mg/m2. Treatment was initially well tolerated, but after the second cycle the patient developed increasing shortness of breath. Computed tomography (CT for staging after the second cycle showed bilateral predominantly interstitial infiltration highly suggestive of acute lung fibrosis. Bronchoscopy revealed signs of chronic bronchitis and watery discharge from both lungs. Bronchoalveolar lavage and transbronchial needle biopsy was performed. Based on histopathologic examination, diagnosis of OP was made. After cessation of docetaxel and initial high dose steroids, the infiltration ameliorated rapidly. This is the second case in the literature that associates docetaxel with rapid onset of bronchiolitis obliterans. Therefore, patients with lung cancer receiving docetaxel who develop respiratory symptoms should be suspected to develop OP.

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

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    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.

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

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    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.

  19. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    Science.gov (United States)

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  20. 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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    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.

  1. Relationship between quality of life and clinical outcomes in advanced non-small cell lung cancer: best supportive care (BSC) versus BSC plus chemotherapy.

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    Thongprasert, S; Sanguanmitra, P; Juthapan, W; Clinch, J

    1999-04-01

    In a prospective randomized study, 287 patients with advanced non-small cell lung cancer (NSCLC) stage IIIb or IV with ECOG performance status (PS) 0-1 or 2 were randomly assigned to receive either best supportive care (BSC) or supportive care plus combination chemotherapy (IEP regimen: ifosfamide 3 gm/m2 IV with mesna uroprotection, epirubicin 60 mg/m2 IV on day 1 and cisplatin 60 mg/m2 IV on day 2; or MVP regimen: mitomycin-C 8 mg/m2, cisplatin 100 mg/m2 IV on day 1, vinblastine 4 mg/m2 IV on days 1 and 15). Serial assessment of Karnofsky performance status (KPS), modified Functional Living Index-Cancer (T-FLIC) and modified Quality of Life-Index (T-QLI) were used to estimate the quality of life. Interviews were done at entry, at the third month and at 2 months post complete treatment. At least two courses of chemotherapy were considered to be adequate for response evaluation. Patients were treated for a total of four to six courses or until progression of disease. Partial response rates were 40 and 41.7% in IEP and MVP arms. Median survival durations were 5.9 and 8.1 months for the IEP and MVP chemotherapy arms, and 4.1 months for BSC (log-rank test: P = 0.0003). One year survival was 13, 29.8 and 39.3% for the BSC, IEP and MVP regimens, respectively. Two years survival was 7.8, 6.4 and 13.1% for the BSC, IEP and MVP regimens, respectively. Improvement in quality of life (QOL) scores at the first, second and third interview were seen in chemotherapy arms only, not in the BSC arm. We conclude that combination chemotherapy improves the quality of life as well as prolonging the survival of patients with advanced NSCLC.

  2. Chemotherapy with or without gefitinib in patients with advanced non-small-cell lung cancer: a meta-analysis of 6844 patients

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hang; ZENG Chao; WANG Li-yang; XIE Hua; ZHOU Jin; DIAO Peng; YAO Wen-xiu

    2013-01-01

    Background Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC),in whom chemotherapy had failed.Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS).This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC.Methods We systematically searched Medline,EmBase,the Cochrane Central Register of Controlled Trials,reference lists of articles,and proceedings of major meetings for relevant literature.Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis.The primary endpoints were OS and PFS.Results Of 182 relevant studies,12 were included in the final analysis,which consisted of 6844 patients with NSCLC.Overall,we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefltinib-free therapy,but this difference was not statistically significant (HR,0.92; 95% C/:0.85-1.00; P=0.051).Furthermore,gefltinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR,0.72; 95% C/ 0.60-0.87,P=0.001).Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR,2.51; 95% C/,1.67-3.78,P <0.001).Rashes,diarrhea,dry skin,pruritus,paronychia,and abnormal hepatic function were more frequent in the gefitinib therapy group.Conclusions Treatment with gefitinib had a clear effect on PFS and ORR,and it might contribute considerably to the OS.Furthermore,there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.

  3. Retrospective analysis of the clinical and demographic variables on the outcomes after second-line treatment in advanced non-small cell lung cancer

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    Sourav Sau

    2013-01-01

    Full Text Available Background: Platinum based doublets chemotherapy are the standard of care for metastatic or advanced non-small cell lung carcinoma. This leads to modest survival advantage and improve quality-of-life. However, patients with advanced or metastatic disease eventually present disease progression and needs second-line systemic therapy in a selected group of patients or other supportive measures. There is very little knowledge available from the literature about the prognostic variables in patients, who receive second-line therapy. Materials and Methods: We retrospectively reviewed 329 patients received second-line treatment from July 2007 to September 2011 in the Department of Radiation Oncology, Burdwan Medical College and Hospital. For statistical analysis, 12 potential prognostic variables included. Univariate and multivariate regression analysis carried out to identify the prognostic variables associated with survival. Results: The results of univariate analysis for overall survival (OS and survival after second-line therapy identified to have prognostic significance: Age, sex, performance status, smoking history, serum lactate dehydrogenase, histopathology, first-line chemotherapy and its response and second-line therapy except the stage at diagnosis and site of failure after first-line therapy. The multivariate Cox regression analysis has shown that only performance and second-line therapy were independent prognostic variables for survival after second-line treatment and above these prognostic factors; age, smoking status and progression free survival also for OS. Conclusion: The performance status has shown consistent result as a prognostic factor in univariate and multivariate analysis for OS and survival after second-line therapy. These findings may also facilitate pretreatment prediction of survival and be used for selecting patients for the correct choice of cytotoxic therapy.

  4. Effect of Brucea Javanica Oil Emulsion Combined with GP Regimen on the Immune Function of Patients with Advanced Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Zhang Yu; Yu Like; Xia Ning

    2014-01-01

    Objective:To observe the effect of Brucea javanica oil emulsion combined with chemotherapy on the immune function of patients with advanced non-small cell lung cancer (NSCLC). Methods:One hundred and fifty-six patients with NSCLC were randomly divided into treatment group (n=82) treated with Brucea javanica oil emulsion combined with GP regimen chemotherapy and control group (n=74) only with GP regimen chemotherapy. The cellular immunity (CD3+, CD4+, CD8+, CD16+CD56+) and humoral immunity (IgG, IgA, IgM, C3, C4) before and after chemotherapy were tested by lfow cytometry (FCM) and biochemical method, respectively. The inlfuences of two treatment methods on the immune function were compared, and clinical efifcacy was evaluated. Results:The remission rates (RRs) were respectively 40.3% and 36.5% in treatment group and control group, without statistical difference (P>0.05). Compared with chemotherapy before, the cellular immune function after chemotherapy decreased in control group (P<0.05),whereas the levels of CD3+, CD4+, CD4+/CD8+ and CD16+CD56+increased signiifcantly in treatment group (P<0.05 orP<0.01). After chemotherapy, the cellular immune function in treatment group was obviously superior to that in control group, whereas there was no statistical signiifcance by comparison to humoral immune indexes between two groups. Conclusion:With similar efifcacy to control group, Brucea javanica oil emulsion combined with GP regimen chemotherapy can improve the cellular immune function of patients with advanced NSCLC and protect the chemotherapy-induced cellular immune function from damage to a certain extent.

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

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    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.

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

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    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.)

  7. Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

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    Chong’an XU

    2011-12-01

    Full Text Available Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung cancer (NSCLC. The aim of this study is to investigate the relationship between X-ray repair cross complementing protein 1 (XRCC1 and X-ray repair cross complementing protein 3 (XRCC3 gene polymorphisms and the chemosensitivity of platinum-based chemotherapy in patients with advanced NSCLC. Methods Genomic DNA were extracted from the sera of a total of 130 patients with advanced NSCLC who received platinum-based chemotherapy. XRCC1 Arg194 Trp, Arg399 Gln, and XRCC3 Thr241 Met were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method, and the relationship between XRCC1 and XRCC3 polymorphisms and chemotherapy sensitivity was analyzed. Results A total of 130 patients with advanced NSCLC received platinum-based chemotherapy, with an overall response rate of 33.8% after two chemotherapy cycles. The XRCC1 194 and 399 genetic polymorphisms, but not XRCC3 241, were found to be related to the chemosensitivity. The objective response rate of the patients with at least one XRCC1 194 Trp allele was 2.5 times higher than that of Arg/Arg genotype carriers (42.1% vs 22.2%, OR=2.545, 95%CI: 1.159-5.590, P=0.020. The objective response rate of the XRCC1 399 Arg/Arg genotype carriers was significantly higher than that of the patients with at least one Gln allele (45.5% vs 21.9%, OR=0.336, 95%CI: 0.156-0.722, P=0.005. Combined effects between XRCC1 194 and XRCC1 399 were observed. The objective response rate of the patients with at least one XRCC1 194 Trp allele and a 399 Arg/Arg genotype was significantly higher than that of patients with 194 Arg/Arg and 399 Arg/Gln genotypes (44.4% vs 18.8%, OR=3.467, 95%CI: 1.223-9.782, P=0.019. Moreover, XRCC1 and XRCC3 have a combined effect in predicting chemosensitivity

  8. 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....

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

    Directory of Open Access Journals (Sweden)

    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

  10. Clinical benefit of gemcitabine plus cisplatin 3-week regimen for patients with advanced non-small cell lung cancer:a prospective observational study

    Institute of Scientific and Technical Information of China (English)

    王莉; 廖美琳; 李龙芸; 万欢英; 徐农; 刘基巍; 梁厚杰

    2004-01-01

    Background Platinum-based chemotherapy has been proved effective in patients with advanced non-small cell lung cancer (NSCLC). This study evaluated the effectiveness and safety of first-line chemotherapy with gemcitabine plus cisplatin (GEM-Cis) 3-week regimen in routine care of Chinese patients with advanced NSCLC.Methods Two hundred and twenty-one patients with NSCLC stage IIIb or IV were enrolled and 209 were eligible foreffectiveness and safety analysis. The median age was 58 (range 29 to 79) years. The percents of cases in stage Ⅳ and stage Ⅲb were 52.2% and 47.8%; of Karnofsky performance score (KPS) less than 80 and 80-100 were 37.3% and 62.7% and of adeno-cancer and non-adeno-cancer were 59.8% and 40.2%. The average number of completed chemotherapy cycles was three. Measures of effectiveness included clinical benefit, significant clinical response (SCR) and adverse effects of GEM-Cis in the treatment of NSCLC at stages Ⅲb/Ⅳ.Results KPS increased from 79±9 at baseline to 86±10 after chemotherapy (P<0.01). Lung cancer symptom scale (LCSS) score of pain, dyspnea and cough increased from 77±24, 74±22 and 63±19 to 92±15, 90±14 and 86±15, respectively (P<0.01). The clinical benefit rate was 85.2% [95% confidence interval (CI) 80.3%-90.0%]. The SCR was 89.5% (95% CI 85.3%-93.7%). Median survival time was 7.8 months (95% CI 7.1 months-9.1 months). Sixty-four patients (30.6%) experienced an adverse effect that was deemed clinically significant. Only one patient (0.5%) was hospitalized due to chemotherapy related adverse effects. Life-threatening toxicity was observed in two patients (1.0%).Conclusion First-line chemotherapy with GEM-Cis in the routine care of Chinese patients with advanced NSCLC is effective and safe.

  11. 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.

  12. Optimizing Treatment Risk and Benefit for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Right Treatment for the Right Patient.

    Science.gov (United States)

    Presley, Carolyn J; Gross, Cary P; Lilenbaum, Rogerio C

    2016-05-01

    The Oncology Grand Rounds series is designed to place original reports published in theJournal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published inJournal of Clinical Oncology, to patients seen in their own clinical practice.A 78-year-old woman with a 40-pack-year smoking history has been referred for treatment of advanced non-small-cell lung cancer. She presented with a persistent cough and worsening dyspnea on exertion. A chest x-ray followed by a chest computed tomography scan revealed a 3-cm right upper lobe mass along with a moderate-size pleural effusion. Pleural fluid cytology was positive for adenocarcinoma. A brain magnetic resonance imaging scan was negative. A reflex molecular profile, includingKRAS,EGFR,ALK,BRAF,HER2,RET,MET, andROS, did not reveal an actionable abnormality. Her past medical history includes diabetes, hypertension, and osteopenia. Her medications include a β-blocker, angiotensin-converting enzyme inhibitor, oral antidiabetic agent, calcium, and vitamin D. The laboratory evaluation is notable for a hemoglobin of 10.8 g/dL and a creatinine clearance of 36 mL/min. The other laboratories are within normal limits. She is somewhat limited by the shortness of breath but maintains an Eastern Cooperative Oncology Group performance status of 1. She is independent in all of her instrumental and basic activities of daily living and denies falls. She has been referred to discuss treatment options.

  13. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC Using Two Different Schedules.

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    Natalia Sutiman

    Full Text Available This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV and metronomic (MSV dosing schedules in patients with advanced non-small cell lung cancer (NSCLC.This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16 and at 100 mg/week in the MSV group (N = 14. Erlotinib was administered orally daily.The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13% and hyponatremia (N = 1; 6% in the CSV group, and neutropenia (N = 5; 36% in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group.Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups.ClinicalTrials.gov NCT00702182.

  14. Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study

    Science.gov (United States)

    Campbell, Toby C.; Zhang, Chong; Kim, KyungMann; Kolesar, Jill M.; Oettel, Kurt R.; Blank, Jules H.; Robinson, Emily G.; Ahuja, Harish G.; Kirschling, Ron J.; Johnson, Peter H.; Huie, Michael S.; Wims, Mary E.; Larson, Martha M.; Hernan, Hilary R.; Traynor, Anne M.

    2014-01-01

    Summary Introduction The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. Methods Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0–2. Patients took vorinostat 400 mg PO daily days 1–14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. Results Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1–6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. Conclusions Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients. PMID:23728919

  15. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

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    Feddock, Jonathan, E-mail: jmfedd0@uky.edu [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States); Arnold, Susanne M. [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States); Department of Medical Oncology, University of Kentucky, Lexington, Kentucky (United States); Shelton, Brent J. [Department of Biostatistics, University of Kentucky, Lexington, Kentucky (United States); Sinha, Partha; Conrad, Gary [Department of Radiology, University of Kentucky, Lexington, Kentucky (United States); Chen, Li [Department of Biostatistics, University of Kentucky, Lexington, Kentucky (United States); Rinehart, John [Department of Medical Oncology, University of Kentucky, Lexington, Kentucky (United States); McGarry, Ronald C. [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States)

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  16. 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

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    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.

  17. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer.

    Science.gov (United States)

    Feng, Kaichao; Guo, Yelei; Dai, Hanren; Wang, Yao; Li, Xiang; Jia, Hejin; Han, Weidong

    2016-05-01

    The successes achieved by chimeric antigen receptor-modified T (CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer (NSCLC). In this phase I clinical study (NCT01869166), patients with epidermal growth factor receptor (EGFR)-positive (>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECIST1.1 and immune- related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR(+) T cells was 0.97×10(7) cells kg(-1) (interquartile range (IQR), 0.45 to 1.09×10(7) cells kg(-1)). Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced relapsed/refractory NSCLC.

  18. XRCC3 Thr241Met is associated with response to platinum-based chemotherapy but not survival in advanced non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Mantang Qiu

    Full Text Available BACKGROUND: A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3 Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC, while the conclusion is still conflicting. MATERIALS AND METHODS: We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs and hazard ratios (HRs and corresponding 95% confidence intervals (95% CIs were used to estimate the association strength. RESULTS: A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116-1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087-2.004, Pheterogeneity = 0.696. This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929-1.261, Pheterogeneity = 0.564, and there was no difference between Asian and Caucasian population. CONCLUSIONS: These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

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

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    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.

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

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    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

  1. Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer

    Science.gov (United States)

    Isla, Dolores; De Castro, Javier; Juan, Oscar; Grau, Santiago; Orofino, Javier; Gordo, Rocío; Rubio-Terrés, Carlos; Rubio-Rodríguez, Darío

    2017-01-01

    Objectives Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR–TKI-related adverse events (AEs) was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS). Methods The frequency of AEs was established from a recently published meta-analysis. In Spain, the daily cost of both drugs can be considered similar; as a result, only the costs of management of the AEs were considered. Costs and resource utilization in the management of the AEs were estimated by a panel of Spanish oncologists and from studies previously carried out in Spain. A probabilistic analysis was performed based on a Monte Carlo simulation. Results The model generated 1,000 simulations. The total cost per patient treated with erlotinib and afatinib was €657.44 and €1,272.15, respectively. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €550.86 and €106.58, respectively, whereas the cost with afatinib was €980.63 and €291.52, respectively. The reduction in the number of AEs with erlotinib could avoid a mean cost for the NHS of €614.71 (95% CI: €342.57–881.29) per patient. Conclusion In advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce health care costs for the NHS, due to a decrease in the AE rate compared with afatinib. In long-term treatments, the avoidance of complications and the lowering of costs associated with the management of AEs are relevant factors that contribute to the sustainability of the health system. PMID:28115857

  2. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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    Hong, C; Ju, S; Ahn, Y [Samsung Medical Center, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.

  3. Relationship between Expression of β-tubulin-Ⅲ Plus Stathmin in Advanced Non-Small Cell Lung Cancer and its Sensitivity to Venorelbine Chemotherapy

    Directory of Open Access Journals (Sweden)

    Xiaolin PU

    2009-01-01

    Full Text Available Background and objective Vinorelbine plus cisplatin/carboplatin (NP is one of the standard combination chemotherapy regimen for advanced non-small cell lung cancer (NSCLC. The aim of this study is toinvestigate the relationship between expression of Stathmin and β-tubulin-Ⅲ in NSCLC biopsies and sensitivity to Vinorelbine, which would provide a basis of the proper medicine choice for the patients' tailored chemotherapy. Methods Western blot was used to investigate the expression of Stathmin and β-tubulin-Ⅲ protein in the biopsies from stage ⅢB-Ⅳ NSCLC patients. All the cases were divided into 4 groups according to the level of the two proteins, of which L represented both protein expressed lowly, B showed β-tubulin-Ⅲ lowly expressed group, while S showed Stathmin lowly, and H represented both protein highly expressed. At the same time, all the patients accepted NP chemotherapy for 2 or 4 cycles according to the responses to this regimen. The responses rate (RR, media survival time (MST, time to progress (TTP were observed. Results A total of 90 stage ⅢB-Ⅳ NSCLC patients were divided into 4 groups, 22 in L group, 23 in B and S group while 22 in H group respectively. The RR of the groups were 68.2%, 26.1%, 30.4% and 22.7% respectively.There were statistically significant differences between L group and other 3 groups (P <0.05. The MST were 377, 305, 321 and 271 days respectively, and the TTP were 240, 182, 190 and 166 days in the 4 groups. Statistically significant differences between L group and other 3 groups (P <0.05 can be seen in both MST and TTP. Conclusion The expression of β-tubulin-Ⅲ and Stathmin in advanced NSCLC biopsies had relationship with the sensitivity to NP chemotherapyregimen in the patients. Cases with high level of these two proteins would have poor responses to this cytotoxic drug.

  4. Clinical Study on Treatment of Advanced Non-small Cell Lung Cancer by Arsenious Acid Combined with Tα-1 Thymus Peptide and Megestrol Acetate

    Institute of Scientific and Technical Information of China (English)

    郭岳峰; 焦智民

    2002-01-01

    Objective:To observe the therapeutic effect of arsenious acid combined with Tα-1 thymuspeptide and megestrol acetate on advanced non-small cell lung cancer. Methods: Nintey-two patients weredivided randomly into the treated group(n= 45) and the control group(n= 47). The treated group weretreated with arsenious acid combined with Tα-1 thymus peptide and megestrol acetate, and the controlgroup were treated with chemotherapy in the NP protocol. Results: (1) Therapeutic effect: In the 36 pa-tients of the treated group, 2 were evaluated as CR, 8 as PR, 9 as MR, 8 as SD and 9 as PD, the CR+PRrate being 27.7% (10/36), while in the 40 patients of the control group, the corresponding numbers were3, 10, 11, 9, 7 and 32.5% (13/40). Comparison between the CR+PR rate between the two groupsshowed insignificant difference (P>0.05). (2)Clinical benefit rate: The positive rate of Karnofsky scoresin the treated group and the control group was 44.4 % and 20.0 % respectively; and the positive rate ofbody weight in the two groups was 33.3 % and 12.5 % respectively, the difference between the two groupswas significant ( all P<0.05). (3)Changes of T- cell subsets and NK cell activity: CD4 and CD4/CD8 ra-tio after treatment in the treated group increased significantly (P<0.05), while in the control group,CD3, CD4, CD4/CD8 ratio and NK cell activity all lowered significantly (P<0.01). Comparison betweenthe two groups after treatment showed significant difference in CD4, CD4/CD8 ratio and NK cell activity,with those in the treated group all higher than those in the control group (P<0.01). (4)Adeverse-reac-tion: No serious adverse reaction was found in both two groups. (5)Median survival period: The treatedgroup was 30 weeks and that in the control group was 28.5 weeks, and the difference between the twogroups was insignificant (P>0.05). Conclusion: Arsenious acid combined with Tα-1 thymus peptide andmegestrol acetate was a relatively effective scheme with low toxicity in

  5. Classification and Regression Tree Analysis of Clinical Patterns to Predict the Survival of Patients with Advanced Non-small Cell Lung Cancer Treated with Erlotinib

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    Yutao LIU

    2011-10-01

    Full Text Available Background and objective Erlotinib is a targeted therapy drug for non-small cell lung cancer (NSCLC. It has been proven that, there was evidence of various survival benefits derived from erlotinib in patients with different clinical features, but the results are conflicting. The aim of this study is to identify novel predictive factors and explore the interactions between clinical variables as well as their impact on the survival of Chinese patients with advanced NSCLC heavily treated with erlotinib. Methods The clinical and follow-up data of 105 Chinese NSCLC patients referred to the Cancer Hospital and Institute, Chinese Academy of Medical Sciences from September 2006 to September 2009 were analyzed. Multivariate analysis of progressive-free survival (PFS was performed using recursive partitioning referred to as the classification and regression tree (CART analysis. Results The median PFS of 105 eligible consecutive Chinese NSCLC patients was 5.0 months (95%CI: 2.9-7.1. CART analysis was performed for the initial, second, and third split in the lymph node involvement, the time of erlotinib administration, and smoking history. Four terminal subgroups were formed. The longer values for the median PFS were 11.0 months (95%CI: 8.9-13.1 for the subgroup with no lymph node metastasis and 10.0 months (95%CI: 7.9-12.1 for the subgroup with lymph node involvement, but not over the second-line erlotinib treatment with a smoking history ≤35 packs per year. The shorter values for the median PFS were 2.3 months (95%CI: 1.6-3.0 for the subgroup with lymph node metastasis and over the second-line erlotinib treatment, and 1.3 months (95%CI: 0.5-2.1 for the subgroup with lymph node metastasis, but not over the second-line erlotinib treatment with a smoking history >35 packs per year. Conclusion Lymph node metastasis, the time of erlotinib administration, and smoking history are closely correlated with the survival of advanced NSCLC patients with first- to

  6. Comparison of three methods for detecting epidermal growth factor receptor mutations in plasma DNA samples of Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    QIN Ling; ZHONG Wei; ZHANG Li; LI Long-yun; WANG Meng-zhao

    2011-01-01

    Background Epidermal growth factor receptor (EGFR) mutations can predict tumor response to tyrosine kinase inhibitors (TKIs). Detecting EGFR mutations in plasma DNA samples in patients with advanced non-small cell lung cancer is challenging and promising. We compared three methods for detecting plasma EGFR mutations, including direct DNA sequencing, denaturing high-performance liquid chromatography (DHPLC) and Scorpions Amplification Refractory Mutation System (Scorpions ARMS).Methods Plasma DNA samples from 73 patients with stage ⅢB to Ⅳ adenocarcinoma were analyzed for EGFR mutations in exons 19 (deletion mutation) and 21(L858R mutation) using direct DNA sequencing, DHPLC and Scorpions ARMS. Sensitivities of the three methods were compared and the relationship between EGFR mutations and patients'survival was analyzed.Results In 73 patients, we detected EGFR mutations in 5 samples (6.9%) by direct DNA sequencing, in 22 samples (30.1%) by DHPLC, and in 28 samples (38.4%) by Scorpions ARMS. EGFR mutations were found in 13 samples in exon 19 and in 9 samples in exon 21 by DHPLC, while we found mutations in 15 samples in exon 19 and in 13 samples in exon 21 by Scorpions ARMS. Among the 73 patients, there was 90.4% concordance between DHPLC and Scorpions ARMS (66/73, K=0.79, P=0.07). Of the 73 patients, 46 patients were treated with gefitinib, including 18 patients with mutations and 28 patients without mutations as determined by Scorpions ARMS. The 18 patients with mutations had a significantly longer progression-free survival (PFS) time (median PFS was 21.0 months) than the 28 patients without mutations (median PFS was 7.0 months) (P=0.022).Conclusions Among the three methods for detecting EGFR mutations in plasma DNA samples of patients with advanced lung adenocarcinoma, direct gene sequencing had the lowest sensitivity, while Scorpion ARMS showed the highest mutation detecting capability. DHPLC is slightly less sensitive than Scorpion ARMS. EGFR

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

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    Wenhua Liang

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR

  8. 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

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    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.

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

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    Hesselius Patrik

    2004-09-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

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

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    Higginson, Daniel S., E-mail: daniel.higginson@gmail.com [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Socinski, Mark A. [Department of Medicine, Division of Hematology and Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States)

    2012-11-01

    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

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

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    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

  12. Comparison of EUS-guided fine needle aspiration and integrated PET-CT in restaging after treatment for locally advanced non-small cell lung cancer

    NARCIS (Netherlands)

    Stigt, Jos A.; Oostdijk, Ad H.; Timmer, Paul R.; Shahin, Ghada M.; Boers, James E.; Groen, HarryJ. M.

    2009-01-01

    Background: After induction treatment restaging of mediastinal disease in patients with stage III non-small cell lung cancer (NSCLC) may lead to selection of candidates for further surgical treatment. Nodal down-staging is the best predictive characteristic for proceeding with surgery. We report our

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

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    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

  14. Sequential (gemcitabine/vinorelbine) and concurrent (gemcitabine) radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

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    Stanzel Sven; Kaiser Hans J; Krohn Thomas; Reinartz Patrick; Pinkawa Michael; Piroth Marc; Gagel Bernd; Breuer Christian; Asadpour Branka; Schmachtenberg Axel; Eble Michael J

    2007-01-01

    Abstract Background The aim of the study was to determine the maximal tolerated dose (MTD) of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC) and to evaluate the efficacy of this regime in a phase II study. Methods 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patien...

  15. Meta-analysis of EGFR tyrosine kinase inhibitors compared with chemotherapy as second-line treatment in pretreated advanced non-small cell lung cancer.

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    Ning Li

    Full Text Available Since efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs versus chemotherapy in the treatment of patients with pretreated advanced non-small cell lung cancer (NSCLC remain controversial, we performed a meta-analysis to compare them.An internet search of several databases was performed, including PubMed, Embase, and the Cochrane database. Randomized trials that compared an EGFR-TKI with chemotherapy in the second-line setting were included. The outcomes were progression-free survival (PFS, overall survival (OS, objective response rate (ORR, and grade 3-4 toxicities. The PFS, OS for the EGFR mutation-positive (EGFR M+ and EGFR mutation-negative (EGFR M- subgroups were pooled. The pooled hazard ratios (HRs and odds ratios (ORs with their corresponding confidence intervals (CIs were calculated on the STATA software.Our meta-analysis combined 3,825 patients from 10 randomized trials. Overall, EGFR-TKIs and second-line chemotherapy have equivalent efficacy in terms of PFS (HR, 1.03; 95%CI, 0.87-1.21; P = 0.73; I2 = 78.7%, Pheterogeneity<0.001, OS (HR, 1.00; 95%CI, 0.92-1.08; P = 0.90; I2 = 0.0%, Pheterogeneity = 0.88, and ORR (OR, 1.34; 95%CI, 0.86-2.08; P = 0.20; I2 = 73.1%, Pheterogeneity<0.001. However, subgroup analysis based on EGFR mutation status showed that second-line chemotherapy significantly improved PFS (HR, 1.35; 95%CI, 1.09-1.66; P = 0.01; I2 = 55.7%, Pheterogeneity = 0.046 for EGFR M- patients, whereas OS was equal (HR, 0.96; 95%CI, 0.77-1.19; P = 0.69; I2 = 0.0%, Pheterogeneity = 0.43; EGFR-TKIs significantly improved PFS (HR, 0.28; 95%CI, 0.15-0.53; P<0.001; I2 = 4.1%, Pheterogeneity = 0.35 for EGFR M+ patients, whereas OS was equal (HR, 0.86; 95%CI, 0.44-1.68; P = 0.65; I2 = 0.0%, Pheterogeneity = 0.77. Compared with chemotherapy, EGFR-TKIs led to more grade 3-4 rash, but less fatigue/asthenia disorder, leukopenia and

  16. Acceptable Safety of Bevacizumab Therapy in Combination with Chemotherapy in Patients with Advanced Lung Cancer

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    Wei WU

    2009-03-01

    Full Text Available Background and objective Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that selectively binds to and neutralizes the biologic activity of human vascular endothelial growth factor (VEGF. Bevacizumab was approved by the U.S. Food and Drug Administration (FDA in October 2006 for use in combination withcarboplatin and paclitaxel for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic,nonsquamous, non-small cell lung cancer (NSCLC. The aim of this study is to observe the safety of bevacizumab therapy in combination with chemotherapy in Chinese patients with NSCLC. Methods Patients with advanced non-squamous NSCLC were treated with Bevacizumab 15 mg/kg, d1, repeated every 21 days until PD; Plus paclitaxel 175 mg/m2, on dl and carboplatin AUC=6 on dl. The cycle was repeated every 21 days. Results One grade 3 epistaxis was observed in onepatient. One grade 4 thrombosis was observed in one patient. 3/4-grade epistaxis and thrombosis was the most significant adverse events. Other adverse effects, such as hemoptysis, hypertension and proteinuria, were not severe and could be well tolerated. Conclusion Most chemotherapy-naive patients with advanced non-squamous NSCLC treated with bevacizumab in combination with paclitaxel and carboplatin have little adverse effects that can be well tolerated.

  17. The relevance of external quality assessment for molecular testing for ALK positive non-small cell lung cancer: results from two pilot rounds show room for optimization.

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    Lien Tembuyser

    Full Text Available Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is a critical biomarker to predict response to tyrosine kinase inhibitors such as crizotinib. To promote high quality testing in non-small cell lung cancer, the European Society of Pathology has introduced an external quality assessment scheme. This article summarizes the results of the first two pilot rounds organized in 2012-2013.Tissue microarray slides consisting of cell-lines and resection specimens were distributed with the request for routine ALK testing using IHC or FISH. Participation in ALK FISH testing included the interpretation of four digital FISH images.Data from 173 different laboratories was obtained. Results demonstrate decreased error rates in the second round for both ALK FISH and ALK IHC, although the error rates were still high and the need for external quality assessment in laboratories performing ALK testing is evident. Error rates obtained by FISH were lower than by IHC. The lowest error rates were observed for the interpretation of digital FISH images.There was a large variety in FISH enumeration practices. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing.

  18. Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation-positive non-small cell lung cancers: an update for recent advances in therapeutics.

    Science.gov (United States)

    Chung, Clement

    2016-06-01

    The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive (improved progression-free survival and improved response rate) when treated with small molecule tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib. The two most common mutations that account for greater than 85% of all EGFR gene mutations are in-frame deletions in exon 19 (LREA deletions) and substitution in exon 21 (L858R). Exon 18 mutations occur much less frequently at about 4% of all EGFR gene mutations. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and 20-40% of Asian patients with non-small cell lung cancer. T790M gene mutation at exon 20 is associated with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Early studies showed that activating EGFR gene mutations are most common in patients with adenocarcinoma histology, women, never smokers and those of Asian ethnicity. A recent multi-center phase III trial suggested that frontline epidermal growth factor receptor tyrosine kinase inhibitor therapy with afatinib is associated with improved progression-free survival compared to chemotherapy regardless of race. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. However, despite a durable response of greater than a year, resistance to epidermal growth factor receptor tyrosine kinase inhibitors inevitably occurs. This mini-review describes the clinically relevant EGFR gene mutations and the efficacy/toxicity of small molecule epidermal growth factor receptor tyrosine kinase

  19. Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer

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    Gabriel Lima Lopes

    2015-08-01

    Full Text Available AbstractLung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21, first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs. Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

  20. Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer *

    Science.gov (United States)

    Lopes, Gabriel Lima; Vattimo, Edoardo Filippo de Queiroz; de Castro, Gilberto

    2015-01-01

    Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC. PMID:26398757

  1. Advances in Lymph Node Metastasis and the Modes of Lymph Node 
Dissection in Early Stage Non-small Cell Lung Caner

    Directory of Open Access Journals (Sweden)

    Ningning DING

    2016-06-01

    Full Text Available Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. Anatomical lobectomy with systematic mediastinal lymph node dissection have been the standard surgical treatment for NSCLC. However, it is controversial in the extent of lymph node dissection for early stage NSCLC. Accurate nodes stage and the extent of mediatinal nodes dissection affect the peri-operative complications and the prognosis of NSCLC greatly. In the past decade, more and more surgeons demostrated that lobe-specific or selective mediastinal lymph node dissection is suitable for clinical stage I NSCLC, especially the stage Ia lesions, and may become the standard lymph node dissection mode in the future.

  2. [Advances in Lymph Node Metastasis and the Modes of Lymph Node 
Dissection in Early Stage Non-small Cell Lung Caner].

    Science.gov (United States)

    Ding, Ningning; Mao, Yousheng

    2016-06-20

    Lung cancer ranks the first position in morbidity and mortality among all malignances in China. Non-small cell lung cancer (NSCLC) accounts for nearly 80% of all lung malignancies. Surgical resection is still the current major treatment method for early stage NSCLC. Lymph node stages together with the extent of lymph node dissection directly affect the prognosis. Anatomical lobectomy with systematic mediastinal lymph node dissection have been the standard surgical treatment for NSCLC. However, it is controversial in the extent of lymph node dissection for early stage NSCLC. Accurate nodes stage and the extent of mediatinal nodes dissection affect the peri-operative complications and the prognosis of NSCLC greatly. In the past decade, more and more surgeons demostrated that lobe-specific or selective mediastinal lymph node dissection is suitable for clinical stage I NSCLC, especially the stage Ia lesions, and may become the standard lymph node dissection mode in the future.

  3. Pemetrexed in Previously Treated Non-small Cell Lung Cancer Patients with Poor Performance Status

    Institute of Scientific and Technical Information of China (English)

    Sun YoungJUNG; Su JinYOO; Ji Young SHIN; Ji Won PARK; Jeong Eun LEE; Hee Sun PARK; Ju Ock KIM; Sun Young KIM

    2011-01-01

    Background and objective Pemetrexed have been approved for the treatment of patients affected by advanced non-small cell lung cancner (NSCLC) in progression after first-line chemotherapy. We evaluated the activity and feasibility of pemetrexed in previously treated NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC were evaluated from April 2007 to March 2009. The patients had relapsed or progressed after prior chemotherapy treatment. Pemetrexed (500 mg/m2) was administered intravenously once every 3 weeks after progression to prior chemotherapy. The tumor response was evaluated according to RECIST criteria by chest CT at every 2 cycles of chemotherapy.Results A total 61 patients were eligible for analysis. Performance status of them (100%) was over 2. The response rate and disease control rate were 14.7% and 37.7% respectively. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (P=0.045) and disease control rate (P=0.008). The median survival time and the median progression free survival (PFS) time were 6.11 months and 2.17 months, respectively. Comparing the efficacy of pemetrexed in these two settings [second-line versus (12/61) more than third (49/61)], there was no significant difference in regard to median survival (11.18 months vs 11.46 months, P=0.922,S), but PFS was more longer in third- or further-line groups than second-line group (1.39 months vs 2.25 months, P=0.015,3).Conclusion Pemetrexed is a feasible regimen in previously treated NSCLC with poor performance status.

  4. 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

    2016-04-21

    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.

  5. Customized Treatment in Non-Small-Cell Lung Cancer Based on EGFR Mutations and BRCA1 mRNA Expression

    Science.gov (United States)

    Rosell, Rafael; Perez-Roca, Laia; Sanchez, Jose Javier; Cobo, Manuel; Moran, Teresa; Chaib, Imane; Provencio, Mariano; Domine, Manuel; Sala, Maria Angeles; Jimenez, Ulpiano; Diz, Pilar; Barneto, Isidoro; Macias, Jose Antonio; de las Peñas, Ramon; Catot, Silvia; Isla, Dolores; Sanchez, Jose Miguel; Ibeas, Rafael; Lopez-Vivanco, Guillermo; Oramas, Juana; Mendez, Pedro; Reguart, Noemi; Blanco, Remei; Taron, Miquel

    2009-01-01

    Background Median survival is 10 months and 2-year survival is 20% in metastatic non-small-cell lung cancer (NSCLC) treated with platinum-based chemotherapy. A small fraction of non-squamous cell lung cancers harbor EGFR mutations, with improved outcome to gefitinib and erlotinib. Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin. RAP80 and Abraxas are interacting proteins that form complexes with BRCA1 and could modulate the effect of BRCA1. In order to further examine the effect of EGFR mutations and BRCA1 mRNA levels on outcome in advanced NSCLC, we performed a prospective non-randomized phase II clinical trial, testing the hypothesis that customized therapy would confer improved outcome over non-customized therapy. In an exploratory analysis, we also examined the effect of RAP80 and Abraxas mRNA levels. Methodology/Principal Findings We treated 123 metastatic non-squamous cell lung carcinoma patients using a customized approach. RNA and DNA were isolated from microdissected specimens from paraffin-embedded tumor tissue. Patients with EGFR mutations received erlotinib, and those without EGFR mutations received chemotherapy with or without cisplatin based on their BRCA1 mRNA levels: low, cisplatin plus gemcitabine; intermediate, cisplatin plus docetaxel; high, docetaxel alone. An exploratory analysis examined RAP80 and Abraxas expression. Median survival exceeded 28 months for 12 patients with EGFR mutations, and was 11 months for 38 patients with low BRCA1, 9 months for 40 patients with intermediate BRCA1, and 11 months for 33 patients with high BRCA1. Two-year survival was 73.3%, 41.2%, 15.6% and 0%, respectively. Median survival was influenced by RAP80 expression in the three BRCA1 groups. For example, for patients with both low BRCA1 and low RAP80, median survival exceeded 26 months. RAP80 was a significant factor for survival in patients treated according to BRCA1 levels (hazard ratio, 1

  6. Single-agent maintenance therapy for advanced non-small cell lung cancer (NSCLC: a systematic review and Bayesian network meta-analysis of 26 randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Qinxue Wang

    2016-10-01

    Full Text Available Background The benefit of maintenance therapy has been confirmed in patients with non-progressing non-small cell lung cancer (NSCLC after first-line therapy by many trials and meta-analyses. However, since few head-to-head trials between different regimens have been reported, clinicians still have little guidance on how to select the most efficacious single-agent regimen. Hence, we present a network meta-analysis to assess the comparative treatment efficacy of several single-agent maintenance therapy regimens for stage III/IV NSCLC. Methods A comprehensive literature search of public databases and conference proceedings was performed. Randomized clinical trials (RCTs meeting the eligible criteria were integrated into a Bayesian network meta-analysis. The primary outcome was overall survival (OS and the secondary outcome was progression free survival (PFS. Results A total of 26 trials covering 7,839 patients were identified, of which 24 trials were included in the OS analysis, while 23 trials were included in the PFS analysis. Switch-racotumomab-alum vaccine and switch-pemetrexed were identified as the most efficacious regimens based on OS (HR, 0.64; 95% CrI, 0.45–0.92 and PFS (HR, 0.54; 95% CrI, 0.26–1.04 separately. According to the rank order based on OS, switch-racotumomab-alum vaccine had the highest probability as the most effective regimen (52%, while switch-pemetrexed ranked first (34% based on PFS. Conclusions Several single-agent maintenance therapy regimens can prolong OS and PFS for stage III/IV NSCLC. Switch-racotumomab-alum vaccine maintenance therapy may be the most optimal regimen, but should be confirmed by additional evidence.

  7. 非小细胞肺癌免疫治疗的研究进展%Advances on Immunotherapy Research in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    施博文; 乔文亮; 韩玉栋; 胡海洋; 陈珮; 林强

    2016-01-01

    肺癌(lung cancer)是全球发病率及死亡率最高的恶性肿瘤之一,非小细胞肺癌(non-small cell lung cancer,NSCLC)占肺癌的85%,其五年生存率只有15%,传统的抗肿瘤治疗方法(手术、放疗和化疗等)在抑制肿瘤进展中的作用有限,即使有手术机会,也有40%以上患者出现局部复发或远处转移.目前多学科治疗较大程度提高了晚期NSCLC的生存期,研究表明,免疫治疗(immunotherapy)可改善肺癌的预后,有望成为肺癌的重要辅助治疗方式.其中,治疗性肿瘤疫苗(vaccination)如MAGE-A3、L-BLP25、Belagenpumatucel-L等、免疫检查点抑制剂(immune checkpoint inhibition)如ipilimumab、nivolumab、pembrolizumab等得到广泛关注.一系列临床试验表明免疫治疗可以使非小细胞肺癌的死亡率得到缓解,本文就其原理、临床试验、不良反应及有待解决问题的临床研究作系统综述.

  8. A phase I study of STEALTH cisplatin (SPI-77) and vinorelbine in patients with advanced non small-cell lung cancer.

    Science.gov (United States)

    Vokes, E E; Gordon, G S; Mauer, A M; Rudin, C M; Krauss, S A; Szeto, L; Golomb, H M; Hoffman, P C

    2000-11-01

    STEALTH cisplatin (SPI-77) is a liposomal formulation of cisplatin that has activity in animal models of non small-cell lung cancer (NSCLC). Vinorelbine has documented clinical activity in NSCLC. The purpose of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of SPI-77 when administered in combination with a fixed dose of vinorelbine to patients with stage IIIB or IV NSCLC refractory to or recurrent following previous chemotherapy. SPI-77 was given on day 1 in combination with vinorelbine at a fixed dose of 25 mg/m2 on days 1 and 8 of a 3-week treatment cycle. Dose escalation of SPI-77 progressed as follows: 20, 40, 80, 100, 120, and 140 mg/m2. Twenty patients were entered (11 men and nine women; median age, 63 years). Sixty-four complete cycles of therapy were administered, and 19 of 20 patients completed at least 1 cycle of combination chemotherapy. Neutropenia was dose limiting at a SPI-77 dose of 140 mg/m2. Neuropathy and nephrotoxicity were minimal and not dose related. A partial response was observed in three of 17 patients eligible for a response evaluation and response duration ranged from 6 weeks to 5 months. In conclusion, treatment with combination SPI-77 and vinorelbine was well tolerated, and our recommended phase II dose is 120 mg/m2 of SPI-77 in combination with vinorelbine at 25 mg/m2. Activity was observed in this patient population, and additional phase II testing of this regimen in a less extensively pretreated cohort of patients with NSCLC is indicated.

  9. 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.

  10. Single-agent maintenance therapy for advanced non-small cell lung cancer (NSCLC): a systematic review and Bayesian network meta-analysis of 26 randomized controlled trials

    Science.gov (United States)

    Zeng, Xiaoning; Ma, Yuan

    2016-01-01

    Background The benefit of maintenance therapy has been confirmed in patients with non-progressing non-small cell lung cancer (NSCLC) after first-line therapy by many trials and meta-analyses. However, since few head-to-head trials between different regimens have been reported, clinicians still have little guidance on how to select the most efficacious single-agent regimen. Hence, we present a network meta-analysis to assess the comparative treatment efficacy of several single-agent maintenance therapy regimens for stage III/IV NSCLC. Methods A comprehensive literature search of public databases and conference proceedings was performed. Randomized clinical trials (RCTs) meeting the eligible criteria were integrated into a Bayesian network meta-analysis. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). Results A total of 26 trials covering 7,839 patients were identified, of which 24 trials were included in the OS analysis, while 23 trials were included in the PFS analysis. Switch-racotumomab-alum vaccine and switch-pemetrexed were identified as the most efficacious regimens based on OS (HR, 0.64; 95% CrI, 0.45–0.92) and PFS (HR, 0.54; 95% CrI, 0.26–1.04) separately. According to the rank order based on OS, switch-racotumomab-alum vaccine had the highest probability as the most effective regimen (52%), while switch-pemetrexed ranked first (34%) based on PFS. Conclusions Several single-agent maintenance therapy regimens can prolong OS and PFS for stage III/IV NSCLC. Switch-racotumomab-alum vaccine maintenance therapy may be the most optimal regimen, but should be confirmed by additional evidence.

  11. Phase I study of celecoxib with concurrent irinotecan, cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ritsuko eKomaki

    2011-12-01

    Full Text Available Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclo-oxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II-III non-small cell lung cancer. Methods and materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea. Grade 3 toxicities were leukopenia (5 patients, fatigue (3, pneumonitis (2, dyspnea (1, pain (1, and esophageal stricture (1. Interestingly, pulmonary fibrosis (a late toxicity was no more severe in the higher-dose (400-mg group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial. Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusions: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue

  12. Phase 2 trial of erlotinib with or without PF-3512676 (CPG 7909, a Toll-like receptor 9 agonist) in patients with advanced recurrent EGFR-positive non-small cell lung cancer.

    Science.gov (United States)

    Belani, Chandra P; Nemunaitis, John J; Chachoua, Abraham; Eisenberg, Peter D; Raez, Luiz E; Cuevas, J Daniel; Mather, Cecile B; Benner, Rebecca J; Meech, Sandra J

    2013-07-01

    This phase 2 study assessed PF-3512676 plus erlotinib in patients with epidermal growth factor receptor-positive advanced non-small cell lung cancer after prior chemotherapy failure. Patients were randomized 1:1 to PF-3512676 (0.20 mg/kg injected subcutaneously once weekly) plus erlotinib (150 mg daily) or erlotinib alone. The primary objective was to estimate progression-free survival (PFS). Patients received PF-3512676 plus erlotinib (n = 18) or erlotinib alone (n = 21). The study was halted because an unplanned interim analysis indicated that large improvement in PFS with addition of PF-3512676 would be unlikely. In the PF-3512676-plus-erlotinib and erlotinib-alone arms, median PFS was 1.6 and 1.7 mo (hazard ratio, 1.00; 95% confidence interval, 0.5-2.0; P = 0.9335), respectively. Salient grade ≥ 3 adverse events in PF-3512676-plus-erlotinib and erlotinib-alone arms were diarrhea (5/0), dyspnea (5/6), fatigue (4/1), other flu-like symptoms (2/0), anemia (2/1), and lymphocytopenia (based on laboratory values, 1/4). Adding PF-3512676 to erlotinib did not show potential for increased progression-free survival over erlotinib alone in patients with advanced recurrent epidermal growth factor receptor-positive non-small cell lung cancer.

  13. Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who under went EGFR-TKI

    Institute of Scientific and Technical Information of China (English)

    Guo-Hao Xia; Ji-Feng Feng; Yun Zeng; Ying Fang; Shao-Rong Yu; Li Wang; Mei-Qi Shi; Wei-Li Sun; Xin-En Huang; Jia Chen

    2014-01-01

    Objective:Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor (EGFR-TKI) compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired resistance over time. hTe mechanisms of resistance are complicated. hTe lack of established therapeutic options for patients atfer a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. hTis study evaluates the inlfuence of EGFR-TKI retreatment following chemotherapy atfer failure of initial EGFR-TKI within at least 6 months on NSCLC patients. Methods:hTe data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. Atfer chemotherapy, the patients were retreated with EGFR-TKI (geiftinib 250 mg qd or erlotinib 150 mg qd), and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were assessed with CT scan. Results:Of the 27 patients who received EGFR-TKI retreatment, 1 (3.7%) patient was observed in complete response (CR), 8 (29.6%) patients in partial response (PR), 14 (51.9%) patients in stable disease (SD), and 4 (14.8%) patients in progressive disease (PD). hTe disease control rate (DCR) was 85.2%(95%CI:62%-94%). hTe median progression-free survival (mPFS) was 6 months (95%CI:1-29). Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. hTe DCR was 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EGFR-TKI, no patient in CR, 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. hTe DCR was 85.7%, and the mPFS was 9.5 months. Signiifcant difference was found between the two

  14. Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Topkan Erkan

    2012-10-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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

  15. 非小细胞肺癌免疫治疗进展%Advances in Immunotherapies for Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    何圆; 尤长宣

    2014-01-01

    Globally, Lung cancer is the leading cause of cancer-related death of high morbidity and mortality with poor prognosis, which needs some more effective and less toxic therapies. hTe immunotherapies offer a novel approach for the treatment of patients with non-small cell lung cancer (NSCLC) in both the adjuvant and palliative disease settings. A number of promising immunotherapies based on different mechanism have now been evaluated showing an increasing response rate. Moreover, further phase II/III clinical trials will be indicated to explore its value. hTese include checkpoint inhibitors (anti-CT-LA4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody), active vaccination (L-BLP25 liposome vaccine, Belagenpumatucel-L vaccine, MAGE-A3 protein vaccine) and adoptive vaccination (CIK cells). hTe purpose of this paper will draw a summary on the theory, clinical trials, toxicity and problems to be solved of the immunotherapies in NSCLC.%肺癌是全球范围内癌性死亡的首要因素,发病率、死亡率高,预后较差,急需开发一种新的高效低毒疗法。作为术后辅助或是姑息治疗手段,免疫治疗为非小细胞肺癌患者提供了一个新的治疗方向。免疫疗法作用机理各不相同,如免疫检测点受体抑制剂(抗CTLA4抗体、抗PD-1抗体、抗PD-L1抗体)、主动性免疫疫苗(L-BLP25脂质体疫苗、Belagenpumatucel-L疫苗、MAGE-A3蛋白疫苗)、过继性免疫疫苗(CIK细胞)等,研究表明免疫治疗非小细胞肺癌肿瘤缓解率较前提高,前景值得期待,II期/III期临床试验亦在进一步探索其临床应用价值。本文就当前非小细胞肺癌免疫疗法原理、临床试验、不良反应及待解决问题作一概述。

  16. 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.)

  17. A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.

    Science.gov (United States)

    Evans, W K; Nixon, D W; Daly, J M; Ellenberg, S S; Gardner, L; Wolfe, E; Shepherd, F A; Feld, R; Gralla, R; Fine, S

    1987-01-01

    One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung cancer [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific nutritional intervention during a 12-week study period when chemotherapy was administered. Those patients randomized to nutritional interventions were counselled to take oral nutrients with caloric intake equal to 1.7 to 1.95 times their basal energy expenditure, depending on their pretreatment nutritional status ("standard" group). An augmented group was counselled to have a caloric intake equivalent to that of the standard group but with 25% of calories provided as protein and additional supplements of zinc and magnesium. Counselling increased caloric intake in both tumor types but reduced weight loss in the short term only for lung cancer patients. Ninety-three NSCLC patients were evaluable for tumor response to vindesine and cisplatin. Overall, only 20.4% of the patients responded, and there were no significant differences in response rates, median time to progression, or overall duration of survival between the nutrition intervention groups and the control group. The tumor response rate to time-sequenced 5-fluorouracil (5-FU) and methotrexate in the 81 evaluable patients with colorectal cancer was only 14.8%, and no significant differences in tumor response rates were noted between the three groups. Furthermore, the median time to progression and overall duration of survival were not different for the control, standard, and augmented groups. Nutritional interventions using dietary counselling had no impact on the percent of planned chemotherapy dose administered, the degree of toxicity experienced by patients, or the frequency of treatment delays. A multivariate prognostic factor analysis demonstrated that for lung cancer, the percent of weight loss, serum albumin concentration, and presence of liver metastases were significant (P less

  18. Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib

    DEFF Research Database (Denmark)

    Sorensen, Boe S; Wu, Lin; Wei, Wen;

    2014-01-01

    BACKGROUND: The feasibility of monitoring epidermal growth factor receptor (EGFR) mutations in plasma DNA from patients with advanced non-small cell lung cancer (NSCLC) during treatment with erlotinib and its relation to disease progression was investigated. METHODS: The amount of EGFR-mutant DNA...... was tested in plasma DNA from patients with advanced NSCLC with allele-specific polymerase chain reaction assays. Blood samples from 23 patients with adenocarcinoma of NSCLC that carried tyrosine kinase inhibitor-sensitizing EGFR mutations were taken immediately before treatment with erlotinib. Additional...... blood samples were taken at timed intervals until erlotinib treatment was withdrawn. RESULTS: The amount of plasma DNA with sensitizing EGFR mutations was found to be reduced after the first cycle of erlotinib treatment in 22 of 23 patients (96%). No patients presented with the resistant T790M mutation...

  19. An Evidence-Based Approach to the Use of Predictive Biomarkers in the Treatment of Non- Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Quinton, Cindy [Juravinski Cancer Centre, 699 Concession, St Hamilton, Hamilton, ON L8V 5C2 (Canada); Ellis, Peter M., E-mail: peter.ellis@jcc.hhsc.ca [Juravinski Cancer Centre, 699 Concession, St Hamilton, Hamilton, ON L8V 5C2 (Canada); Department of Oncology, McMaster University Hamilton, ON L8S 4L8 (Canada)

    2011-09-13

    Recent advances in the treatment of non-small cell lung cancer (NSCLC) have led to improvements in patient survival and quality of life. It is unclear whether molecular abnormalities associated with NSCLC cell survival, growth and proliferation are useful in predicting treatment benefit. We conducted a systematic review to establish which biomarkers contribute meaningfully to the management of NSCLC. A team of researchers searched PubMed and conference proceedings (ASCO, ESMO, IASLC, USCAP) using MESH terms for NSCLC and randomized trials (RCT), plus keywords for variables of interest. Evidence from multiple RCTs confirmed that histologic subtype is prognostic for survival and predictive of treatment efficacy and/or toxicity in NSCLC. Likewise, activating mutations of the epidermal growth factor receptor (EGFR) are associated with benefit from EGFR tyrosine kinase inhibitors in patients with advanced non-squamous NSCLC and should be assessed routinely. No biomarkers to date reliably predict response to anti-Vascular Endothelial Growth Factor (VEGF) therapies. There are inconsistent data on the role of ERCC1, BRCA, Beta tubulin III, RRM1, K-RAS, or TP-53 in treatment decisions. These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established. Personalized care of patients with NSCLC based on biomarkers is increasingly important to both clinical practice and research.

  20. A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer

    OpenAIRE

    Chiappori, A. A.; Kolevska, T.; Spigel, D. R.; Hager, S.; Rarick, M; Gadgeel, S; Blais, N.; von Pawel, J.; Hart, L; Reck, M.; Bassett, E.; Burington, B.; Schiller, J H

    2014-01-01

    Imetelstat, a novel telomerase inhibitor, failed to improve significantly median PFS and OS as maintenance therapy (±bevacizumab) in advanced NSCLC. Telomere length (TL) biomarker results were consistent with the hypothesis that telomerase inhibition is of greater benefit to patients with tumors possessing shorter telomeres; the patients with shorter TL had a trend toward longer median PFS and OS.

  1. 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

    reaction (qRT-PCR) and immunohistochemistry (IHC). MATERIALS AND METHODS: Analyses of IGF1R were performed on patients with advanced NSCLC, included in a randomized chemotherapy trial, having large, representative tissue samples. IGF1R mRNA and protein expression were correlated to clinical end-points...

  2. New approaches for individual treatment of advanced non-small cell lung cancer%晚期非小细胞肺癌患者个体化治疗的新突破

    Institute of Scientific and Technical Information of China (English)

    陆舜

    2011-01-01

    Lung cancer continues to be the leading cause of cancer death worldwide, and non-small cell lung cancer is the most common type of lung cancer. Despite many clinical trials of platinum-based chemotherapy in combination with various drugs, the median survival time of patients with non-small cell lung cancer remains poor. The overall 5-year survival rate of patients with advanced non-small cell lung cancer is approximately 15%, and has improved only marginally in recent years.A recent milestone in this field has been the development of molecular-targeting drugs, among which gefitinib and erlotinib targeting the epidermal growth factor receptor (EGFR) have improved the efficacy of therapy for non-small cell lung cancer.Anti-angiogenetic drug, such as bevacizumab, has been used in the treatment of non-small cell lung cancer. Moreover, the discovery of echinoderm microtubule-associated protein-like 4/anaplastic lymphoma kinase(EMI4-ALK) fusion gene has contributed to the marvelous progress in research of lung cancer. In this review, the drugs used in individualized treatment of advanced non-small cell lung cancer, such as EGFR-tyrosine kinase inhibitors and EMIA-ALK fusion gene inhibitors are introduced.%在世界范围内,肺癌位居所有癌症致死的首位,且其中大部分为非小细胞肺癌.尽管大量有关含铂化疔或联合其他药物的临床研究不断涌现,非小细胞肺癌患者的预后仍然差强人意.晚期非小细胞肺癌患者的5年生存率约为15%,在过去几年中未有明显提高.目前,肺癌治疗领域的主要成就在于靶向治疗的出现,例如针对表皮细胞生长因子受体(EGFR)靶点的吉非替尼和厄罗替尼,以及针对抗血管内皮细胞生长因子(VEGF)的贝伐单抗,均广泛运用于临床.同时,关于棘皮动物微管相关蛋白样/间变淋巴瘤激酶(EML4-ALK)融合基因的研究使得肺癌的治疗又有了新的进展.该文主要对晚期非小细胞肺癌患者个体化治疗

  3. [A meta-analysis of platinum plus docetaxel or vinorelbine in the first-line treatment of advanced non-small cell lung cancer].

    Science.gov (United States)

    Liu, Taisheng; Wu, Hua; Zhuang, Xianmian; Lu, Di; Cai, Ruijun; Wang, Wujun

    2014-04-01

    背景与目的 以铂类为基础联合第三代药物的双药化疗方案是治疗晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的标准一线治疗方案。本研究采用meta分析的方法评价多西他赛联合铂类(docetaxel plus platinum, DP)方案对比长春瑞滨联合铂类(vinorelbine plus platinum, VP)方案治疗晚期NSCLC的疗效和安全性。方法 计算机检索Pubmed、EMBASE、Cochrane Library、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、中文科技期刊全文数据(VIP)库及万方数据库关于DP方案与VP方案治疗晚期NSCLC的随机对照试验(randomized controlled trial, RCT)。根据Cochrane Handbook 5.1.0的质量评价标准,用Stata 12.0软件进行统计学分析。结果 研究共纳入7项RCTs,包括晚期NSCLC患者2,381例。DP方案的2年生存率(HR=0.887, 95%CI: 0.810-0.972, P=0.010)、有效率(RR=1.276, 95%CI: 1.107-1.450, P=0.001)和腹泻发生率(RR=3.134, 95%CI: 1.918-5.121, P<0.001)较VP方案高;DP方案减少了贫血的发生率(RR=0.386, 95%CI: 0.311-0.478, P<0.001);DP方案与VP方案在1年生存率、白细胞减少、中性粒细胞减少、血小板减少、厌食、恶心、呕吐方面的差异无统计学意义。结论 DP方案虽然增加了腹泻发生率,但却减少了贫血的发生率,同时提高了2年生存率和有效率。相比VP方案,DP方案可能更适合一线治疗晚期NSCLC。

  4. [Relationship between BIM gene polymorphism and therapeutic efficacy in the retreatment of advanced non-small cell lung cancer with tyrosine kinase inhibitor].

    Science.gov (United States)

    Zheng, Lei; Lin, Baochai; Song, Zhengbo; Xie, Fangjun; Hong, Wei; Feng, Jianguo; Shao, Lan; Zhang, Yingping

    2013-12-01

    背景与目的 BIM基因是BCL-2家族成员之一,是参与细胞死亡的重要介质。在非小细胞肺癌(non-small cell lung cancer, NSCLC)中,BCL-2家族成员蛋白介导的EGFR基因突变癌细胞能够激活PI3K/AKT/mTORC和MER/ERT信号通道,决定着细胞的存活或者凋亡。BIM基因的BH3域缺失,则容易引起凋亡受阻。本研究通过检测BIM基因多态性,探讨其与复治晚期NSCLC表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor, EGFR-TKI)治疗疗效的关系。方法 入选2009年1月1日-2012年10月1日就诊于浙江省肿瘤医院的123例复治晚期NSCLC患者,所有患者既往均接受过化疗,失败后接受吉非替尼或厄洛替尼靶向治疗。采用多聚酶链反应方法检测患者外周血白细胞中BIM基因多态性。采用SPSS 13.0统计软件分析。结果 在疾病控制率上, BIM基因无多态性的患者较BIM基因有多态性的患者呈略好趋势(DCR 75.5% vs 57.1%, χ2=2.931, P=0.087)。单因素分析中位PFS,女性长于男性(6.9个月 vs 4.5个月,χ2=7.077,P=0.008);不吸烟者长于有吸烟史者(8.0个月 vs 2.5个月,χ2=15.277,P0.05)。结论 BIM基因多态性的有无对复治晚期NSCLC EGFR-TKI治疗患者的中位无进展时间有统计学差异,检测患者BIM基因多态性对复治晚期NSCLC EGFR-TKI治疗患者的评估预后有重要意义。

  5. MicroRNA-related single-nucleotide polymorphism of XPO5 is strongly correlated with the prognosis and chemotherapy response in advanced non-small-cell lung cancer patients.

    Science.gov (United States)

    Geng, Ji-Qun; Wang, Xiao-Chen; Li, Long-Fei; Zhao, Jun; Wu, Song; Yu, Gui-Ping; Zhu, Kou-Jun

    2016-02-01

    This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all

  6. Combination of radiotherapy and chemotherapy in locally advanced non-small cell lung cancer%局部晚期非小细胞肺癌的放化综合治疗

    Institute of Scientific and Technical Information of China (English)

    胡劲

    2009-01-01

    The main methods to treat locally advanced non-small cell lung cancer are radiotherapy and chemotherapy. The combination of radiotherapy and chemotherapy includes sequential chemoradiotherapy and concurrent chemoradiotherapy. The effectiveness of concurrent chemoradiotherapy is superior to that of sequential chemoradiotherapy, but the toxicity of concurrent chemoradiotherapy increases as well. Continuing to explore new ways which can improve the effectiveness and reduce the toxicity is the current and future direction. [Key words] Carcinoma, non-small cell lung; Radiotherapy; Drug therapy%局部晚期非小细胞肺癌主要的治疗方式是放疗和化疗.放疗与化疗结合分为序贯放化疗和同步放化疗两种.同步放化疗在治疗疗效方面优于序贯治疗,但同时增加了不良反应.继续探索新的提高疗效、降低毒性的方法是目前及未来的研究方向.

  7. 83例局部晚期非小细胞肺癌同步放化疗临床分析%Clinical analysis of concurrent chemoradiotherapy in 83 patients with locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Zhihua Sun; Qinfeng Li; Zhenyu Li; Yeshan Chen; Yao Jiang; Gang Wu

    2012-01-01

    Objective: The purpose of this study was to evaluate the efficacy and safety of concurrent chemoradiotherapy (CCRT) in patients with locally advanced non-small cell lung cancer (LANSCLC). Methods: 83 cases of patients who have been diagnosed for locally advanced NSCLC by determined cytology or pathology were divided into two groups randomly, 42 patients in NP group and 41 patients in EP group. All patients accepted thoracic three-dimensional conformal radiotherapy (3D-CRT) and concurrent either NP chemotherapy in NP group or EP chemotherapy in EP group. 3D-CRT were started on day 1 in the first cycle of chemotherapy. Chemotherapy were carried out for 4 cycles, every cycle was 21 days. Thoracic radiotherapy adopted conventional fractionated irradiation with 15 MeV-X ray, a total dose of 60 Gy. Results: In 83 patients were evaluable, there were 5 cases complete regression to be observed, 29 cases had partial regression (PR), 7 cases with stable disease (SD) and 1 case with progression disease (PD) in NP group. CR 3 cases, PR 27 cases, SD 9 cases and PD 2 cases in EP group. The overall response rate (RR) both NP group and EP group were 80.9%, 73.2%, respectively (P = 0.785).1-, 2-, 3-year survival rate were 90.5%, 69.0%, 28.6% and 82.9%, 51.2%, 21.9%, respectively (P = 0.393). The incidence of leukopenia and thrombocytopenia in NP group was higher than that in the EP group (P < 0.05). Conclusion: CCRT in patients with locally advanced non-small cell lung cancer, 3D-CRT with concurrent NP or EP chemotherapy. 1-, 2-, 3-year overall survival (OS) and average survival time (AST) were not statistically differences, a higher incidence of toxicities were observed in NP group but can be tolerable.

  8. Observation and nursing care of Locally advanced non small cell lung cancer treated with intratumoral bruceajavanica oil injection%鸦胆子油乳瘤内注射治疗LANSCLC疗效观察与护理

    Institute of Scientific and Technical Information of China (English)

    陈华; 刘敏

    2013-01-01

    目的:探讨鸦胆子油乳瘤内注射治疗不可手术切除局部晚期非小细胞肺癌的疗效及护理.方法:对284例不可手术切除局部晚期非小细胞肺癌患者采用瘤内注射鸦胆子油乳,并配合有效护理,观察疗效及不良反应.结果:完全缓解(CR)20例,部分缓解(PR)126例,好转(MR)76例,稳定(SD)46例,进展(PD)16例,有效率51.4%.无进展生存期(PFS)11.31月.结论:加强鸦胆子油乳瘤内注射治疗不可手术切除局部晚期非小细胞肺癌注射前后的健康指导和护理,可显著提高疗效.%Objective:To investigate the intratumoral injection of Brucea javanica oil in the treatment of no operation resection for locally advanced non small cell lung cancer and nursing care. Methods:284 cases of no operation resection of locally advanced non small cell lung cancer with intratumoral injection of Brucea javanica oil, combined with effective nursing, observation curative effect and adverse reaction. Results:The complete response ( CR ) in 20 cases, partial remission ( PR ) in 126 cases,76 cases improved ( MR ), stability ( SD ) in 46 cases, progress (PD) in 16 cases, with an efficiency of 51.4%. Progression free survival ( PFS ) in 11.31months. Conclusion:Strengthening of Brucea Javanica Oil intratumor injection for treatment of no operation resection of locally advanced non small cell lung cancer before and after injection of health guidance and care, can significantly improve the efficacy.

  9. 局部晚期非小细胞肺癌不同化放疗顺序的临床疗效%The clinical effect of the different order of radiotherapy for locally advanced non small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    张朝辉

    2015-01-01

    目的:比较局部晚期非小细胞肺癌(NSCLC)患者不同放疗顺序效果。方法:2011年8月-2014年8月收治局部晚期NSCLC患者62例,按照完全抽样法1:1分成两组,每组31例;对照组予4个周期化疗再序贯放疗,研究组予先放疗再接受4个周期化疗,比较不同化疗顺序的临床疗效。结果:治疗后,研究组完成全部治疗时间和疾病进展时间均短于对照组(P<0.05)。结论:局部晚期NSCLC患者予先放疗再接受4个周期化疗可缩短治疗时间,延长疾病的进展时间。%Objective:To compare the clinical effect of the different order of radiotherapy for locally advanced non small cell lung cancer(NSCLC).Methods:62 patients with locally advanced non small cell lung cancer were selected from August 2011 to August 2014,they were divided into two groups with 31 cases in each;the control group was treated with 4 cycles of chemotherapy combined with radiotherapy,the study group received radiotherapy and then received 4 cycles of chemotherapy,to compare the clinical effect of different chemotherapy order.Results:After treatment,the study group to complete a full treatment time and time to disease progression were shorter than the control group(P<0.05).Conclusion:Patients with locally advanced non small cell lung cancer received radiotherapy and then received 4 cycles of chemotherapy can shorten the treatment time,prolonged time to progression of the disease.

  10. Efficacy of DC-CIK combined with chemotherapy in the treatment of advanced non small cell lung cancer%DC-CIK联合化疗治疗晚期非小细胞肺癌的疗效分析

    Institute of Scientific and Technical Information of China (English)

    张士法

    2016-01-01

    Objective:To investigate the therapeutic effect of DC-CIK combined with chemotherapy in patients with advanced non-small cell lung cancer.Methods:120 patients with advanced non small cell lung cancer were selected.They were divided into two groups.The control group was treated with chemotherapy alone.The observation group was treated with DC-CIK combined with chemotherapy.The treatment effect and adverse reaction of the two groups were compared.Results:The effective rate of the observation group was significantly higher than that of the control group,and the incidence of adverse reactions was significantly lower than that of the control group(P<0.05).Conclusion:DC-CIK combined with chemotherapy in the treatment of advanced non-small cell lung cancer can significantly improve the patient's treatment effect,enhance the ability to resist cancer,and reduce the incidence of adverse reactions.%目的:探讨 DC-CIK 联合化疗在晚期非小细胞肺癌中的治疗效果。方法:收治晚期非小细胞肺癌患者120例,分两组,对照组给予单纯化疗治疗,观察组给予DC-CIK联合化疗治疗,比较两组患者的治疗效果和不良反应的发生情况。结果:观察组的治疗有效率明显高于对照组,不良反应的发生率明显低于对照组(P<0.05)。结论:DC-CIK联合化疗在晚期非小细胞肺癌的治疗中,能够明显提高患者的治疗效果,增强抗肿瘤能力,减少不良反应的发生。

  11. The influence of autologous cytokine-induced killer cell treatment on the objective efficacy and safety of gefitinib in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shuxian Qu; Zhaozhe Liu Co-first author; Zhendong Zheng; Zhenyu Ding; Tao Han; Fang Guo; Jianing Qiu; Xiaodong Xie ; Dongchu Ma 

    2015-01-01

    Objective The aim of the study was to observe the influence of autologous cytokine-induced kil er cel (CIK) treatment on the objective ef icacy and safety of gefitinib in advanced non-smal cel lung cancer (NSCLC). Methods Sixty-six patients with NSCLC received gefitinib as second-line treatment. They were randomly divided into 2 groups, and informed consent forms were signed before grouping. Gefitinib was administrat-ed to the control group, and autologous CIK treatment was added to the observation group. The objective treatment and adverse reactions were evaluated in both groups. Results The objective response rate (ORR) and the disease control rate (DCR) of the observation group were slightly higher than those of the control group, although no statistical dif erences were found between the 2 groups (P > 0.05). The incidences of diarrhea, fatigue, anorexia, oral ulcers, and myelosuppression in the observation group were much lower than those in the control group (P 0.05). Conclusion Autologous CIK in combination with gefitinib is ef ective as second-line treatment for ad-vanced NSCLC, and can significantly reduce adverse reactions and improve the objective ef icacy.

  12. Effectiveness and safety of pemetrexed for non-small cell lung cancer in the Andalusian Public Health System

    Directory of Open Access Journals (Sweden)

    María Antonia Pérez-Moreno

    2016-11-01

    Full Text Available Objective: To evaluate effectiveness and safety profile of pemetrexed in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC when it´s used on real clinical practice in Andalusia (a Spanish region with 8.5 million inhabitants, 2014 census data. Methods: An observational multicentre retrospective study was conducted. Adult patients with locally advanced/metastatic NSCLC who received pemetrexed in any hospital in the Andalusian Public Health System during the last term of 2011 were included. We collected patients´ baseline characteristics, diagnostic and treatment data, effectiveness variables (response to treatment with pemetrexed and overallsurvival and main adverse reactions detected. Results: 172 patients from 17 hospitals were included (77.33% were men, median age 63 years old (between 34 and 83. The predominant histology was adenocarcinoma (84.30% and 85.20% were diagnosed of lung cancer with IV-stage. 78.49% had been smokers at some point in their lives. Median overall survival from the start of pemetrexed was 9 months (95%CI, 4.1-13.9. Progression of the disease was the most frequent response (33.14%, only one patient had complete response. Stable disease was associated with a higher probability of survival. Main adverse reactions detected were asthenia, haematological reactions, gastrointestinal reactions and termal o mucous toxicity. No patients discontinued treatment for serious toxicity. Conclusions: Pemetrexed resulted quite effective in NSCLC when it was used on real clinical practice, with higher survival in non-squamous histology and patients with the best score of Eastern Cooperative Oncology Group scale. The toxicity profile was well tolerated. Prospective studies would be needed to confirm the effect of prognostic factors observed

  13. Maintenance therapy in advanced non-small cell lung cancer%晚期非小细胞肺癌维持治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    程婷婷; 杨谨

    2011-01-01

    目的:总结维持治疗在晚期非小细胞肺癌中的研究进展,探讨维持治疗的意义.方法:应用PubMed和CNKI期刊全文数据库检索系统,以“NSCLC maintenance therapy及非小细胞肺癌,维持治疗”为关键词,共检索到2001-2011年相关文献284篇,纳入分析25篇.结果:维持治疗是近年来为延长晚期NSCLC患者生存期并提高其生存质量而出现的新的治疗观点,目前已有多项临床试验证实标准一线化疗结束使疾病获得控制后,继续给予维持治疗可以显著延长患者的无疾病进展生存期(progression-free survival,PFS),部分药物可以显著延长总生存(overall survival,OS),患者耐受良好.结论:维持治疗可以使晚期NSCLC患者获益,但是其最终疗效和患者的病理类型、EGFR突变状况、体力状况和对药物的耐受情况密切相关,结合患者的实际情况,进行个体化治疗,是NSCLC患者未来治疗的方向.%OBJECTIVE; To summarize the advances of maintenance therapy in NSCLC, and discuss the significance of this therapeutic method. METHODS; The full text database of PubMed and CNKI were searched, and the words " NSCLC ( maintenance therapy" were used as key words. Totally 284 related articles were retrieved between the year of 2001 and 2011 in all, then 25 were analyzed. RESULTS; Maintenance therapy emerged as a new viewpoint in these years in order to prolong the overall survival and to improve quality of life for patients with advanced NSCLC. At present,many clinical trials have demonstrated that the patients with advanced NSCLC who achieved CR.PR and SD after the first-line chemotherapy could be significantly prolonged Progression-free survivaKPFS) and overall survivalCOS) if they received continued maintenance therapy. The tolerance was well. CONCLUSIONS: Patients with advanced NSCLC can benefit from the maintenance therapy. However, the final therapeutic effect is closely related to the pathological type,EGFR mutation, physical

  14. Our experiences with erlotinib in second and third line treatment patients with advanced stage IIIB/ IV non-small cell lung cancer.

    Science.gov (United States)

    Mehić, Bakir; Stanetić, Mirko; Tinjić, Ljuljeta; Smoljanović, Vlatka

    2008-11-01

    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 open-label, 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).

  15. Prognostic score for second-line chemotherapy of advanced non-small-cell lung cancer: external validation in a phase III trial comparing vinflunine with docetaxel.

    Science.gov (United States)

    Di Maio, Massimo; Krzakowski, Maciej; Fougeray, Ronan; Kowalski, Dariusz M; Gridelli, Cesare

    2012-07-01

    A prognostic index for second-line chemotherapy of NSCLC was previously developed, based on individual patient data (IPD) of nine randomized trials. In order to validate the prognostic score in an external dataset, we analysed IPD of a non-inferiority phase III trial comparing vinflunine vs. docetaxel in second-line treatment of advanced NSCLC. Primary endpoint of this analysis was overall survival (OS). The following variables were considered for survival analysis and score calculation: gender, performance status, stage of disease, tumour histology, type of first-line treatment, response to first-line treatment. Cox model, stratified by treatment arm, was used for multivariate analysis. Individual prognostic scores were derived, and patients were divided into 3 categories: 9 (worst). All 551 patients enrolled in the trial had complete information for the calculation of prognostic score. Median OS in the whole group was 6.9 months, with similar efficacy in the two treatment arms. Median OS was 12.9, 6.9 and 3.8 months in the best, intermediate and worst category, respectively. Cox model showed a significant effect comparing intermediate vs. best category (Hazard Ratio 1.79, 95%CI 1.31-2.47, p=0.0003) and comparing worst vs. best category (Hazard Ratio 3.25, 95%CI 2.18-4.83, pmodel was high (0.926), indicating a good discrimination according to the proposed three risk categories. Prognostic ability of our score for candidates to second-line treatment in advanced NSCLC was successfully validated, allowing the identification of subgroups of patients with more vs. less favourable outcome. Prognostic score could be useful in daily decision-making in clinical practise, because a better understanding of factors conditioning life expectancy of patients could greatly help a careful evaluation of risks and benefits associated with therapeutic decisions.

  16. 吉非替尼在晚期非小细胞肺癌维持治疗的作用%Effect of gefitinib on maintenance therapy of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘爱华; 陆京伯; 苏瑾

    2010-01-01

    目的 观察吉非替尼对既往化学治疗有效的晚期(Ⅳ期)非小细胞肺癌维持治疗的疗效和安全性.方法 在15例经病理学确诊的非小细胞肺癌经4~6个周期含铂类方案化疗后取得临床完全缓解和部分缓解患者中,随机选取2例Ⅳ期肺腺癌患者予以吉非替尼维持治疗,250 mg/次,1次/d,口服.结果 2例晚期非小细胞肺癌患者肺部肿瘤进一步缩小,胸腔积液、心包积液消失.病例1放射性核素骨显像示转移病灶放射性浓聚程度明显降低.病例2 MRI显示颅内多发转移病灶稳定.患者生活质量显著提高,KPS评分提高30,症状改善率达100%.不良反应为皮疹和腹泻(Ⅰ级),不需处理.结论 吉非替尼用于既往化疗显效的晚期非小细胞肺癌患者的维持治疗有较好的疗效和安全性.同时可改善患者的相关症状,提高生活质量.%Objective To observe the efficacy and safety of gefitinib on maintenance therapy in patients with advanced (grade Ⅳ ) non-small cell lung cancer after effective chemotherapy. Methods Among 15 patients with non-small cell lung cancer confirmed pathologically who obtained complete response or partial response after 4-6 cycles of chemotherapy, two patients with advanced (grade Ⅵ) adenocarcinoma of lung were randomly selected to be administered gefitinib for maintenance therary, 250 mg,orally once a day. Results In two patients with advanced non-small cell lung cancer, lung tumor reduced further, pleural effusion and pericardial effusion disappeared. Radionuclide bone imaging of the first patient showed that radioactivity level of metastatic lesion reduced. Magnetic resonance imaging of the second patient showed that multiple intracranial metastatic lesions were stable. The quality of life improved significantly,KPS score increased by 30,and the improvement rate of symptom was 100%. The adverse reactions were rash and diarrhea (grade Ⅰ ) ,without treatment. Conclusions Gefitinib is

  17. First line chemotherapy with planned sequential administration of gemcitabine followed by docetaxel in elderly advanced non-small-cell lung cancer patients: a multicenter phase II study

    Science.gov (United States)

    Tibaldi, C; Vasile, E; Antonuzzo, A; Di Marsico, R; Fabbri, A; Innocenti, F; Tartarelli, G; Amoroso, D; Andreuccetti, M; Dico, M Lo; Falcone, A

    2008-01-01

    This multicenter phase II study evaluated, in chemonaive patients with stage IIIB–IV NSCLC, age ⩾70 and with a performance status 0–2, the activity, efficacy and tolerability of planned sequential administration of gemcitabine 1200 mg m−2 on days 1 and 8 every 3 weeks for three courses followed by three cycles of docetaxel 37.5 mg m−2 on days 1 and 8 every 3 weeks, provided there was no evidence of disease progression. A total of 56 patients entered the study. According to intention-to-treat analysis, the objective response rate was 16.0% (95% CI 7.6–28.3%); 23 patients (41.0%) had stable disease and 24 patients (43%) had progressive disease. Five patients who had a stable disease after three courses of gemcitabine obtained a conversion to partial response by docetaxel. Median time to progression was 4.8 months (95% CI 3.6–6.0 months) and median duration of survival was 8.0 months (95% CI 5.6–10.5 months). The 1-year survival rate was 34%. No grade 4 haematological toxicity was observed and grade 3 neutropenia and thrombocytopenia were reported in 5.4 and 3.6% of the patients, respectively. Grade 3/4 mucositis and grade 3 diarrhoea, both occurred in 3.6% of the patients and grade 3 asthenia was observed in 9% of patients. One patient reported a grade 4 skin toxicity. No treatment-related deaths occurred. Sequential gemcitabine and docetaxel is a well-tolerated and effective regimen in elderly advanced NSCLC patients. PMID:18212755

  18. Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

    Directory of Open Access Journals (Sweden)

    Abdulaziz eAl Farsi

    2014-06-01

    Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

  19. 吉非替尼在晚期非小细胞肺癌靶向治疗中的疗效观察%Gefitinib in the Treatment of Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    袁云

    2012-01-01

    Objective To observe the clinical efficacy and drug-related toxicities of Gefitinib in the treatment of ad vanced non-small cell lung cancel NSCLC ). Methods 16 patients with advanced non-small cell lung cancer diagnosed histolog-ically or cytologically were treated with Gefitinib ( at a dose of 250 mg,per day,orally ) until the disease progression or intolerable toxicities. Results All the 16 patients were evaluable. The overall response rate was 31. 2% , including 0%( 0/16 ) patient with complete response and 31. 2%( 5/16 ) patients with partial response. 43. 8% ( 7/16 ) patients had stable disease and 25.0% ( 4/ 16 ) patients had progressive disease, so the disease control rate is 75. 0%. The median overall survival time ( OS ) was 4. 8 months and the 1-year survival rate was 18. 7% . Drug related adverse reactions included skin rash,diarrhea,xerosiscutis,increas ing level of transaminases, ulcer. 2 patients stopped the treatment due to intolerable diarrhea. Conclusion Gefitinib is effective in the treatment of advanced non-small cell lung cancer obout overall survival, can significantly relieve NSCLC-related symptoms. The toxicities are mild and tolerable. Treatment with Gefitinib could be considered as one of the therapies to advanced non-small cell lung cancer.%目的 探讨吉非替尼(Gefitinib)治疗晚期非小细胞肺癌的有效性及安全性.方法 16例晚期非小细胞肺癌患者采用吉非替尼(250 mg,每天1次,口服)治疗,直至出现疾病进展或发生不可耐受的不良事件.结果 16例均可评价疗效,CR为0%(0/16),PR为31.2%(5/16),SD为43.8%(7/16),PD为25.0%(4/16);客观缓解率(RR)为31.2%,疾病控制率(DCR)为75.0%.中位生存期4.8个月,1年生存率为18.7%.与药物相关的不良反应依次为:皮疹、腹泻、皮肤干燥、转氨酶升高、溃疡.其中有2例患者因腹泻对症治疗不佳而停药.结论 吉非替尼可让既往治疗失败的晚期NSCLC患者生存受益,且不良反应轻,耐受性良好,

  20. 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

  1. Prognostic value of the standardized uptake value maximum change calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography imaging in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Jin F

    2016-05-01

    Full Text Available Feng Jin,1,2 Hui Zhu,2 Zheng Fu,3 Li Kong,2 Jinming Yu2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, 3Department of Nuclear Medicine, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, People’s Republic of China Purpose: The purpose of this study was to investigate the prognostic value of the standardized uptake value maximum (SUVmax change calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography (PET imaging in patients with advanced non-small-cell lung cancer (NSCLC.Patients and methods: We conducted a retrospective review of 115 patients with advanced NSCLC who underwent pretreatment dual-time-point 18F-fluorodeoxyglucose PET acquired at 1 and 2 hours after injection. The SUVmax from early images (SUVmax1 and SUVmax from delayed images (SUVmax2 were recorded and used to calculate the SUVmax changes, including the SUVmax increment (ΔSUVmax and percent change of the SUVmax (%ΔSUVmax. Progression-free survival (PFS and overall survival (OS were determined by the Kaplan–Meier method and were compared with the studied PET parameters, and the clinicopathological prognostic factors in univariate analyses and multivariate analyses were constructed using Cox proportional hazards regression.Results: One hundred and fifteen consecutive patients were reviewed, and the median follow-up time was 12.5 months. The estimated median PFS and OS were 3.8 and 9.6 months, respectively. In univariate analysis, SUVmax1, SUVmax2, ΔSUVmax, %ΔSUVmax, clinical stage, and Eastern Cooperative Oncology Group (ECOG scores were significant prognostic factors for PFS. Similar results were significantly correlated with OS, except %ΔSUVmax. In multivariate analysis, ΔSUVmax and %ΔSUVmax were significant

  2. 艾迪注射液对晚期非小细胞肺癌NP方案化疗的影响%Effects of Aidi injection on vinorelbine plus cisplatin chemotherapy for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Ximing Xu; Wei Ge; Guangjin Yuan

    2008-01-01

    Objective: To evaluate the effects of Aidi injection on vinorelbine plus cisplatin (NP) chemotherapy for advanced non-small cell lung cancer (NSCLC). Methods: Ninety eight patients with advanced NSCLC were randomized to receive either NP alone or NP plus Aidi injection every 3 weeks. The primary endpoint was overall survival; secondary endpoints included overall response rate, time to progression, and safety. Results: The median overall survival time was 11.6 months in NP plus Aidi-treated patients and 10.1 months in NP alone-treated ones, and 1- and 2-year survival rates were higher in the former (47% and 22%) than the latter (42% and 15%). The overall response rates in Aidi injection plus NP-treated patients tended to be higher but not statistically significant compared with NP alone-treated ones. The occurrence rates of grades 3 or 4 toxicities, e.g. fatigue, nausea, vomiting, appetite loss, leucopenia, thrombocytopenia and anemia, were lower in Aidi injection plus NP-treated patients than NP alone-treated ones, although not significantly different between them. Conclusion: Aidi injection promotes NP chemotherapeutic effects, reduces the toxicities, and improves the patients' tolerance to chemotherapy as well. It may be an effective adjunct to chemotherapy in patients with NSCLC.

  3. Bibliometric Analysis on Traditional Chinese MedicineTreatment for Mid-advanced Non-small Cell Lung Cancer%中医药治疗中晚期非小细胞肺癌文献计量分析

    Institute of Scientific and Technical Information of China (English)

    陆颖; 李洁; 陈驰; 许玲

    2015-01-01

    Objective To discuss the clinical research status of traditional Chinese medicine treatment for mid-advanced non-small cell lung cancer based on literature analysis.Methods Clinical research articles about TCM treatment for mid-advanced non-small cell lung cancer were retrieved from PubMed, Cochrane Library, Web of Science, EBSCOhost, ScienceDirect, CBM, CNKI, VIP and Wanfang Data in March 6, 2014. RCTs and Q-RCTs were identified by retrieving. Metrology analysis was conducted from the aspects of publication time, article sources, publication organizations, cooperation and trial types, with a purpose to discuss the research status of this domain.ResultsTotally 432 articles were considered to be eligible for inclusion. The number of articles was on the rise. Academic journals were the most important sources of these articles. Publication organizations in Guangdong, Shanghai and Beijing produced the most articles. Cooperative researches increased, especially the cooperation between the same research units/universities. Research quality of RCT is increasing.Conclusion The quantity and quality of clinical researches on TCM treatment for mid-advanced non-small cell lung cancer have improved in different degrees. This domain shows great research prospect.%目的:基于文献分析探讨国内中医药治疗中晚期非小细胞肺癌的临床研究现状。方法计算机检索PubMed、Cochrane Library、Web of Science、EBSCOhost、ScienceDirect、中国生物医学文献数据库(CBM)、中国知识资源总库(CNKI)、中文科技期刊数据库(VIP)、万方数据库中有关中医药治疗中晚期非小细胞肺癌临床研究文献,检索时间2014年3月6日。筛选符合纳入标准的随机、半随机临床对照试验,从发文时间、文献来源、发文机构、合作情况、试验类型5方面进行计量学分析,探讨本领域的科研状况。结果共432篇文献符合纳入标准。文献数量总体呈上升趋势,学术期刊是文

  4. GP方案引起NSCLC患者糖耐量异常的临床研究%Clinical Study of Glucose Levels in Patients with Advanced Non-small Cell Lung Cancer Treated by GP Regimen

    Institute of Scientific and Technical Information of China (English)

    姚兰; 蒋成霞; 徐勇; 叶序卷; 贾钰铭; 雷开键; 唐元英

    2015-01-01

    Objective To evaluate blood glucose differences before and after three cycles of chemotherapy in patients with advanced non-small cell lung cancer. Methods 44 patients with advanced non-small cell lung cancer conducted blood routine,bi-ochemical,and C-reactive protein test;Normal blood glucose group treated chemotherapy with GP 3 cycles,high blood sugar groups measured blood glucose by oral glucose tolerance test,then were on diets,exercised or injected insulin. After GP regimen of 3 cy-cles,blood analysis,biochemical,C-reactive protein,oral glucose tolerance test,c-peptide and insulin release test were measured. Results After 3 cycles of GP,25%(8/32) of patients with normal glucose appears abnormal,and half of patients with abnormal glucose tolerance turn into diabetic. After chemotherapy,aspartate aminotransferase and C-reactive protein were significantly differ-ent from the patients with increased blood glucose and normal blodd glucose,the difference was statistically significant(P<0. 05). Conclusion GP regimen could cause glucose metabolism disorders in some patients with advanced non-small cell lung cancer and even induce diabetes. Patients with abnormal aspartate aminotransferase and C-reactive protein are susceptible to elevate blood glu-cose.%目的:分析非小细胞肺癌晚期患者GP方案化疗3周期前后血糖的差异。方法将44名非小细胞肺癌晚期患者根据血糖情况分为血糖正常组和血糖升高组:血糖正常组32例患者直接用GP方案化疗3周期,血糖升高组12例患者予以饮食、运动及胰岛素干预后,再进行GP方案化疗3周期,化疗前后行口服葡萄糖耐量试验、C肽及胰岛素释放试验。结果化疗前血糖正常者经GP方案化疗3周期后25%(8/32)的患者出现血糖升高,而糖调节受损患者化疗后出现一半的患者转变为糖尿病患者。化疗后血糖升高者与血糖正常者比较谷草转氨酶及C反应蛋白差异有统计学意义(P<0.05)

  5. Clinical Developments for the EGFR-TKI Combined with Radiotherapy in Advanced Non-small Cell Lung Cancer%EGFR-TKI联合放疗治疗晚期非小细胞肺癌的研究进展

    Institute of Scientific and Technical Information of China (English)

    李夏南; 朱广迎

    2014-01-01

    肺癌是全球最常见的恶性肿瘤之一,严重威胁人类生命。近年来,以表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs)为首的靶向药物在肺癌治疗中取得巨大进展。因其具有高选择性和低毒性的优势,目前已成为IV期非小细胞肺癌(non-small cell lung cancer, NSCLC)EGFR突变患者的一线治疗方案。然而随着临床的广泛应用,继发耐药成为临床亟待解决的问题。近年来,基础研究证实, EGFR-TKI具有放射增敏性,理论上二者联合不但可以解决放疗后期肿瘤的放射抵抗以及EGFR-TKI继发耐药,还可以增加对肿瘤杀伤能力,同时副反应较同步放化疗小。因此,EGFR-TKI与放疗联合成为晚期NSCLC(IIIb期/IV期)极具探索的治疗模式。本文就EGFR-TKI与放疗联合治疗晚期NSCLC的基础与临床研究进展进行综述。%Lung cancer is one of the most common malignant tumor in the world, severely threatening human life. Recently, targeted therapy such as the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) made huge progress in treatment of lung cancer. EGFR-TKIs, with its high selectivity and low toxicity, is the ifrst choice for EGFR-mutated patients in stage IV non-small cell lung cancer (NSCLC). However, secondary drug resistance becomes a clinical problem to be urgently resolved. In recent years, a series of preclinical studies showed that EGFR-TKI can enhance the antitumor activ-ity of ionizing radiation. hTerefore, EGFR-TKI combined with radiation is extremely promising therapy pattern for advanced NSCLC. hTis review will discuss the research status in EGFR-TKI and radiotherapy for advanced NSCLC.

  6. 克里唑替尼治疗晚期非小细胞肺癌的临床研究进展%Clinical Research of Crizotinib in Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    朱海波; 徐小玉; 王玲

    2013-01-01

    At present,in the treatment of non-small cell lung cancer (NSCLC),targeted therapy has an important status.After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs),crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC.Phase Ⅰ and Ⅱ clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients,little side-effect,and well tolerated.Recently,crizotinib can inhibit ROS1 receptor tyrosine kinase and show extraordinary significant antitumor activity in ROS1-rearranged NSCLC.Drug resistance also exists in crizotinib.The mechanism of drug resistance needs further research.In this study,a review is performed in the mechanism and pharmacokinetics of crizotinib,and the clinical progress of treatment in advanced NSCLC.%目前在非小细胞肺癌(non-small cell lung cancer,NSCLC)的治疗中,靶向药物治疗占有举足轻重的地位.继表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI)之后,针对棘皮动物微管相关蛋白4-间变性淋巴瘤激酶(echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase,EML4-ALK)融合基因突变为靶点的克里唑替尼(crizotinib)成为了NSCLC靶向治疗领域的焦点.Ⅰ期、Ⅱ期临床试验均已证实:crizotinib治疗EML4-ALK阳性晚期NSCLC患者有效,并能改善患者症状,毒副作用小,患者耐受性较好.近期发现crizotinib对ROSI受体酪氨酸激酶也具有抑制作用.Crizotinib在ROS1基因重排NSCLC中显示出了非常明显的抗肿瘤活性.与其它TKIs一样,crizotinib也存在耐药现象,其耐药机制待进一步研究.现就crizotinib作用机制、药代动力学及治疗晚期NSCLC的临床研究进展做一综述.

  7. Research progresses of targeted therapy on advanced non-small cell lung cancer%晚期非小细胞肺癌靶向治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    孙虎; 张俊萍

    2016-01-01

    肺癌恶性程度高,是目前发病率和死亡率居首位的恶性肿瘤,其中非小细胞肺癌约占肺癌的80%~85%,且多数患者在确诊时已属晚期。随着对肿瘤发病机制及其生物学行为研究的不断深入,以特异性高、不良反应轻为特点的分子靶向治疗成为目前关注的焦点,如针对 EGFR、KRAS及EML4-ALK融合基因等常见突变基因的靶向治疗。但是由于基因检测技术、组织标本获取困难等多种原因,致使大约70%以上的晚期非小细胞肺癌患者不能够接受基因靶向治疗,本文就晚期非小细胞肺癌靶向治疗进行综述。%Lung cancer is high malignant, with the most morbidity and mortality currently, including non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancer, and most patients are diagnosed at advanced stage. With the deepening research of tumor pathogenesis and biological behavior, molecular targeted therapy characterized by highspecificity and mild adverse reactions has become the focus of current concern, such as the therapy targeted at EGFR, KRAS, and EML4-ALK fusion genes mutations. However, due to genetic testing, tissue samples and other difficulties, resulting in over about 70% of advanced NSCLC patients can not accept targeted gene therapy. This article reviewed the targeted therapy of advanced NSCLC.

  8. Qiyu particles in advanced non small cell lung cancer treatmentefficacy evaluation in%芪蓣颗粒在晚期非小细胞肺癌治疗中的疗效评价

    Institute of Scientific and Technical Information of China (English)

    王洪艳; 贾文魁

    2013-01-01

    Objective to observe the curative effect of Qiyu granule in the treatment of advanced non small cell lung cancer. Methods according to the inclusion criteria, a total of 75 cases were collected, which were divided into three groups, chinese medicinegroup were given Qiyu pellet orally, chemotherapy group with GPchemotherapy, chemotherapy combined with chinese traditional medicine group with the combination of the above scheme.Conclusion the traditional chinese medicine group Qiyu granule could relieve the clinical symptoms of advanced lung cancer,improve the quality of life;can delay tumor development, improve the survival of patients with advanced lung cancer;chemotherapy,can improve the o bjective response rate of chemotherapy, reduce the toxicity of chemotherapy, which play a synergistic effect attenuated.%目的:观察芪蓣颗粒治疗晚期非小细胞肺癌的疗效。方法按照纳入标准,收集病例75例,将病例分成三组,中药组给予芪蓣颗粒口服,化疗组采用GP方案化疗,中药加化疗组结合以上方案。结果中药组结论:芪蓣颗粒能够缓解晚期肺癌临床症状,改善生存质量;能够延缓肿瘤发展,提高晚期肺癌病人生存期;配合化疗,能够提高化疗的客观缓解率,减轻化疗毒副反应,即起到减毒增效作用。

  9. Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non-small cell lung cancer.

    Science.gov (United States)

    Franchina, Tindara; Amodeo, Valeria; Bronte, Giuseppe; Savio, Giuseppina; Ricciardi, Giuseppina R R; Picciotto, Maria; Russo, Antonio; Giordano, Antonio; Adamo, Vincenzo

    2014-01-01

    Pemetrexed has been widely used in patients with advanced non-small cell lung cancer (NSCLC). The clinical relevance of polymorphisms of folate pathway genes for pemetrexed metabolism have not been fully elucidated yet. The aim of this study was to evaluate the expression levels of circulating miR-22, miR-24, and miR-34a, possibly involved in folate pathway, in NSCLC patients treated with pemetrexed compared with healthy controls and to investigate their impact on patient clinical outcomes. A total of 22 consecutive patients with advanced NSCLC, treated with pemetrexed-based chemotherapy and 27 age and sex matched healthy controls were included in this preliminary analysis. miR-22, miR-24, and miR-34a targets were identified by TargetScan 6.2 algorithm, validating the involvement of these microRNAs in folate pathway. MicroRNAs were isolated from whole blood and extracted with miRNAeasy Mini Kit (Qiagen). miRNA profiling was performed using Real-Time PCR. SPSS 17 was used to data analysis. miR-22, miR-24, and miR-34a were found upregulated (P<0.05) in NSCLC patients versus healthy controls. Higher expression levels were recorded for miR-34a. Nevertheless, significantly higher miR-22 expression was observed in patients developing progressive disease (P=0.03). No significant associations with clinical outcome were recorded for miR-24 and miR-34a. Albeit preliminary, these data support the involvement of miR-22, miR-24, and miR-34a in advanced NSCLC. The correlation between high expression of miR-22 in whole blood and the lack of response in pemetrexed treated NSCLC patients indicates that miR-22 could represent a novel predictive biomarker for pemetrexed-based treatment.

  10. Current status of combined chemo-radiotherapy for locally advanced non-small cell lung cancer%局部晚期非小细胞肺癌同期放化疗研究进展

    Institute of Scientific and Technical Information of China (English)

    吕冬婕; 韩春; 王澜

    2009-01-01

    放化综合治疗是局部晚期非小细胞肺癌(NSCLC)的基本治疗策略.近期研究表明同期放化疗在生存率等方面优于序贯治疗,已成为局部晚期NSCLC的标准治疗模式,但是尚无具体放化结合模式指导临床治疗.为了进一步提高治疗疗效,目前临床研究主要集中于以下几个方面:同期放化治疗加入诱导或巩固化疗、同期放化疗中放疗分割方式的改变、同期放化疗中化疗方式及方案的选择、同期放化疗加入分子靶向治疗.%Combination of chemotherapy and radiotherapy is foundational treatment approach for locally advanced non- small cell lung cancer (NSCLC) patients. Concomitant chemo-radiotherapy have been demons-trated to be better than sequential chemoradiotherapy in survival rate, and it is considered as a standard approach in patients with locally advanced NSCLC. However, the chemo-radiotherapy regimens remain uncert-ain. The main clinical researches aiming at improving the survival rate of locally advanced NSCLC patients are the addition of induction or consolidation, the alteration of radiation fractionation, the alteration of chemo schema and the inte- gration of molecularly targeted therapies combining with concurrent chemo-radiotherapy.

  11. 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 ...

  12. 克唑替尼在ALK阳性中晚期非小细胞肺癌中的疗效观察%Efficacy of crizotinib in advanced ALK positive non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    朱礼阳; 许春伟; 于忠和

    2016-01-01

    目的:探讨克唑替尼治疗晚期间变淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因阳性中晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的近期疗效及毒副反应。方法:回顾性分析43例ALK阳性的中晚期NSCLC患者,服用克唑替尼治疗,服用至病情进展或出现不可耐受的毒副反应,随访12个月,观察疗效。结果:克唑替尼治疗ALK阳性NSCLC的疾病控制率(disease control rate,DCR)为93%(3/43),客观缓解率(objective response rate,ORR)为62%(26/43),中位无进展生存时间(progression free survival,PFS)为7.0个月(95% CI,6.0~8.0月),不良反应主要为消化道症状,其次是谷丙转氨酶升高,视觉障碍,大部分为1~2级。结论:克唑替尼作为NSCLC患者的多靶点靶向治疗,具有良好的疗效及安全性,不良反应轻微。%Objective: To explore clinical effcacy and side effects of crizotinib in advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer.Methods: Retrospectively analysed 43 cases of ALK positive NSCLC patients, receiving oral treatment with crizotinib (250 mg) twice daily until the progress of the disease or the emergence of the side effects. Clinical effcacy was observed atfer 12-month followed-up.Results: hTe DCR of the patients treated with crizotinib was 93% (3/43), ORR was 62% (26/43), and median PFS was 7.0 months (95% CI, 6.0~8.0 months). hTe most frequent treatment-related AEs were gastrointestinal disturbance, followed by increased glutamic-pyruvic transaminase, vision disorder, and most toxicities were grade 1 and 2.Conclusion: Crizotinib, as targets for NSCLC patients with targeted therapy, has good effect and safety, minor adverse reactions.

  13. 吉西他滨联合奈达铂治疗晚期非小细胞肺癌的临床观察%Gemcitabine Combined with Nedaplatin in the Treatment of Advanced Non-small Cell lung Cancer

    Institute of Scientific and Technical Information of China (English)

    兰四友; 张德芬; 邓述恺; 王荣丽; 杨小琼

    2014-01-01

    Objective To observe the efficacy and the side-effects of gemcitabine ( GEM ) combined with nedaplatin (NDP) in the treatment of advanced non -small cell lung cancer(NSCLC). Methods 65 patients with NSCLC were treat with gemcitabine (GEM 1000-1250mg/m2,ivdrip,d1,d8) plus nedaplatin (NDP 80-90mg/m2,ivdrip,d1),every 28 days. Results Five patients out of 65 were complete response,22 patients were partial response,28 patients were stable,10 patients were progres-sive. The objective response rate was 41. 54%, and disease control rate was 84. 62%. The main side-effect was myelosuppres-sion,and no patient was dead in the treatment. Conclusion Domestic gemcitabine plus nedaplatin was an effective treatment with less side-effects.%目的:观察吉西他滨( GEM)联合奈达铂( NDP)组成的GN方案治疗晚期非小细胞肺癌( NSCLC,Non-small cell lung cancer )的疗效和安全性。方法65例NSCLC患者采用GN方案:GEM1000~1250mg/m 2,第1、8d静脉滴注, NDP 80~90mg/m2,第1d 静脉滴注,28d 为1周期。结果全组65例中,完全缓解5例(7.69%),部分缓解22例(33.85%),稳定28例(43.08%),进展10例(15.38%),客观缓解率为41.54%,疾病控制率84.62%。主要不良反应为骨髓抑制,经对症处理后可以缓解,无治疗相关死亡。结论国产吉西他滨联合奈达铂治疗晚期NSCLC疗效较好,不良反应轻。

  14. 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)

    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

    Background 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. Methods Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg 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. Results 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). Conclusions 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. Trial Registration ClinicalTrials.gov NCT02486354 PMID:26599904

  15. Glufosfamide administered by 1-hour infusion as a second-line treatment for advanced non-small cell lung cancer; a phase II trial of the EORTC-New Drug Development Group.

    Science.gov (United States)

    Giaccone, G; Smit, E F; de Jonge, M; Dansin, E; Briasoulis, E; Ardizzoni, A; Douillard, J-Y; Spaeth, D; Lacombe, D; Baron, B; Bachmann, P; Fumoleau, P

    2004-03-01

    The activity of glufosfamide (beta-D-glucosylisophosphoramide mustard) was tested in a multicentre phase II clinical trial in patients with advanced non-small cell lung cancer (NSCLC) who had received one prior line of platinum-based chemotherapy. Patients were treated with 5000 mg/m(2) glufosfamide by a 1-h intravenous (i.v.) infusion every 3 weeks following registration at the European Organisation for Research and Treatment of Cancer (EORTC) Data Center. Patients were randomised between hydration and no hydration to evaluate the nephroprotective effects of forced diuresis. Patients experiencing >/= 35 micromol/l increase of serum creatinine compared with baseline values were taken off the treatment. The Response evaluation criteria in solid tumours (RECIST) criteria were applied for the response assessment. Blood sampling was performed for a pharmacokinetic analysis. 39 patients from seven institutions were registered and a median of three cycles was given (range 0-6) cycles; 20 patients were randomised to the hydration arm. Haematological toxicity was mild, but treatment-related metabolic and electrolytic abnormalities and increases of serum creatinine occurred in several patients. Hydration did not have any significant influence on the plasma pharmacokinetics of glufosfamide and did not show any nephroprotective effect. Only one confirmed partial remission was observed (response rate 3%; 95% (Confidence Interval (CI) 0-14) and 18 cases with stable disease (49%) were recorded as assessed by an independent panel. Median survival of all patients treated was 5.8 months (95% CI 4.2-7.9). In conclusion, glufosfamide administered by a 1-h infusion every 3 weeks has modest activity in advanced NSCLC patients after one prior platinum-based chemotherapy.

  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

    Directory of Open Access Journals (Sweden)

    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. Application value of Cisplatin chrono-chemotherapy for Advanced Non-small Cell Lung Cancer%顺铂时辰化疗在晚期 NSCLC 治疗中的应用价值

    Institute of Scientific and Technical Information of China (English)

    徐成伟; 陈威龙

    2014-01-01

    Objective To evaluate the clinical value and toxicities of cisplatin chrono-chemotherapy for advanced non-small cell lung cancer ( NSCLC) .Methods 64 patients with advanced NSCLC were divided into chrono-chemotherapy group and conventional chemotherapy group .Clinical efficacy and toxicities of the 2 groups were evaluated .Results There was no signifi-cant difference in total response rate between chrono-chemotherapy group ( 53.13%) and conventional chemotherapy group (50.00%).The rates of leucopenia and neutropenia in chrono-chemotherapy group were 9.38%(3/32)and 9.38%(3/32);and the rates of leucopenia and neutropenia in conventional chemotherapy group were 40.63%(13/32) and 37.50%(12/32), there was significant difference between the 2 groups(P<0.05).The rate of gastrointestinal toxicity (nausea) in chrono-chemo-therapy group and in conventional chemotherapy group were 18.75%(6/32)and 62.50%(20/32),there was statistical difference (P<0.05).Conclusion Efficacy of cisplatin chrono-chemotherapy and conventional chemotherapy for advanced non -small cell lung cancer has no difference ,but chrono-chemotherapy has less adverse reactions ,and it is superior to conventional chemothera-py.%目的:探讨顺铂时辰化疗在晚期非小细胞肺癌( NSCLC)治疗中的临床应用价值及不良反应。方法选择晚期NSCLC患者64例,根据数字随机法将患者分为时辰化疗组和常规化疗组,各32例,评价2组临床应用价值和不良反应的差异。结果有效率时辰化疗组为53.13%,常规化疗组为50.00%,2组差异无统计学意义( P>0.05)。时辰化疗组严重白细胞下降者及严重中性粒细胞下降者分别为9.38%(3/32)、9.38%(3/32),常规化疗组分别为40.63%(13/32)、37.50%(12/32),差异有统计学意义(P<0.05)。消化道副作用(恶心)发生者,时辰化疗组为18.75%(6/32),常规化疗组为62.50%(20/32),

  18. The early predictive value of a decrease of metabolic tumor volume in repeated {sup 18}F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Wei, E-mail: weihuang@mcw.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Liu, Bo; Fan, Min [Department of Internal Medicine Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhou, Tao [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Fu, Zheng [PET/CT center, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhang, Zicheng; Li, Hongsheng [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Li, Baosheng, E-mail: alvinbird@163.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China)

    2015-03-15

    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 [{sup 18}F] fluorodeoxyglucose positron emission tomography/computed tomography ({sup 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 {sup 18}F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who

  19. Activity of topotecan given intravenously for 5 days every three weeks in patients with advanced non-small cell lung cancer pretreated with platinum and taxanes: a phase II study.

    Science.gov (United States)

    Gonzalez, Emilio Esteban; Villanueva, Noemi; Fra, Joaquin; Berros, Jose Pablo; Jimenez, Paula; Luque, María; Muñiz, Isabel; Blay, Pilar; Fernandez, Yolanda; Vieitez, José María; Muriel, Carolina; Sanmamed, Miguel; Coto, Pablo Pardo; Izquierdo, Marta; Estrada, Enrique; Lacave, Angel J

    2011-12-01

    Topotecan, a semi-synthetic camptothecin analogue with topoisomerase I interaction, has shown to be an active agent in the treatment of advanced refractory lung cancer. This paper describes the authors' experience with this drug when used as a single agent in patients (pts) with advanced non-small cell lung cancer (NSCLC) refractory to platinum- and taxane-containing chemotherapy regimens. Thirty-five patients with NSCLC refractory to previous chemotherapy and KI ≥ 60% were included in the study. Their characteristics are as follows: median age of 52 years (range 43-69) and Karnofsky PS of 70 (60-80); 27 were male and 8 were female. Twenty-one (60%) patients had adenocarcinoma; eleven (31.4%), squamous cell, and three (8.5%), undifferentiated carcinoma. There was a median of two disease sites and two prior chemotherapy regimens. Topotecan was administered at a dose of 1.25 mg/m(2) I.V. daily for 5 days, repeated every 21 days until disease progression, maximal response, or intolerable toxicity. After 73 cycles, patients received a median of 2 treatment cycles (1-9). All patients except one were considered evaluable for toxicity; eight episodes (24%) of nausea/vomiting and two episodes (6%) of grade 1-2 asthenia, respectively, were reported. Four (12%) patients developed grade 1-2 anemia and two (6%) subjects suffered grade 3 anemia. Seven (21%) patients had grade 1-2 neutropenia and one (3%) presented grade 5 neutropenia. In 33 patients evaluable for activity of the 35 subjects included in the study; one (2.8%) presented a partial response; nine (25.7%) had stable disease, and 23 (65.7%) exhibited disease progression. Median time to progression and overall survival were 54 (12-210) and 70 (12-324) days, respectively. Intravenous topotecan at that dose and administration schedule displays scant activity in terms of response rate in individuals with advanced NSCLC previously treated with platinum and taxanes. The role and usefulness of chemotherapy in this setting

  20. Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.

    Science.gov (United States)

    Chun, Stephen G; Hu, Chen; Choy, Hak; Komaki, Ritsuko U; Timmerman, Robert D; Schild, Steven E; Bogart, Jeffrey A; Dobelbower, Michael C; Bosch, Walter; Galvin, James M; Kavadi, Vivek S; Narayan, Samir; Iyengar, Puneeth; Robinson, Clifford G; Wynn, Raymond B; Raben, Adam; Augspurger, Mark E; MacRae, Robert M; Paulus, Rebecca; Bradley, Jeffrey D

    2017-01-01

    Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports

  1. Prophylactic Cranial Irradiation in Local Advanced Non Small-Cell Lung Cancer: Result from A Multi Center Clinical Trial from German%局部晚期非小细胞肺癌患者的预防性脑照射——来自德国的多中心临床试验结果

    Institute of Scientific and Technical Information of China (English)

    樊旼; 徐崇锐

    2008-01-01

    @@ 1 文献来源 ①Stuschke BM,Eberhardt W,P(o)ttgen C,et al.Prophylactic cranial irradiation in locally advanced non-small-cell lung cancer after muhimodality treatment:Long-term follow-up and investigations of late neuropsychologic effects[J].J Clin Oncol,1999,17:2700-2709.

  2. 四个第三代含铂联合化疗方案在晚期非小细胞肺癌中的比较%Comparison of four third generation platinum-contained chemotherapy regimens for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    杨学宁; 吴一龙

    2003-01-01

    @@ 1文献类型 治疗 2证据水平 1b 3文献来源 Schiller J H, Harrington D, Belani C P, et al. theEastern Cooperative Oncology Group. Comparison ofFour Chemotherapy Regimens for Advanced Non-Small-Cell Lung Cancer [J]. N Eng J Med,2002,346(2):92-98

  3. 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)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. 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.

  5. 晚期非小细胞肺癌 EGFR-TKI 获得性耐药机制%Acquired resistance mechanisms of EGFR-TKI in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    郑悦; 魏素菊

    2015-01-01

    Since the development of molecular biology,the treatment of advanced non-small cell cancer is shifting from traditional chemotherapy into molecular targeted therapy with genotyping as a guide′s help.The most widely used is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).With the appli-cation of EGFR-TKIs,the resistances to EGFR inhibitors are paid more and more attention,in recent years. The main mechanisms of acquired resistances are as follows:secondary mutation of the EGFR gene,amplifica-tion of c-MET,Her2 and other target genes,histological transformation,activation of the bypass mechanisms, loss of p53,the relief of negative feedback loops,overlap of mechanisms,etc.%随着分子生物学的发展,晚期非小细胞肺癌的治疗由传统的化疗转向以基因分型为指导的分子靶向治疗。其中应用较多的是表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)类药物。然而EGFR-TKI 的耐药问题近年来受到越来越多的关注,其机制主要有 EGFR 基因二次突变,c-MET、人类表皮生长因子受体2(Her2)等靶基因的扩增,组织表型的改变,旁路途径的激活,p53基因的缺失,细胞信号通路负反馈的减弱以及多重机制叠加等。

  6. Research progress on target therapy of advanced non-small cell lung cancer%晚期非小细胞肺癌靶向治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    姜文丽; 黄才国

    2016-01-01

    生物标志物检测使得许多晚期非小细胞肺癌(NSCLC)患者获益。近年来,针对表皮生长因子受体(EGFR)和间变性淋巴瘤激酶(ALK)突变呈阳性的NSCLC患者,以吉非替尼、厄洛替尼、阿法替尼为代表的表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)和以克唑替尼为代表的ALK-TKI取得了卓越的疗效。但是,大多数第一代EGFR-TKI和ALK-TKI的疗效因为不可避免的继发性耐药而被减弱。目前,第三代EGFR-TKI正是基于第二代EGFR-TKI的耐药机制研发而成。除此之外,还有许多针对其他突变位点的晚期NSCLC维持治疗的靶向抑制剂。遗憾的是,针对突变比例最大的K-RAS突变,尚无疗效确切的靶向药物。因此,基于肿瘤驱动基因突变机制的探索和靶向药物的开发是目前NSCLC的研究热点。%Detection of biomarkers benefited many advanced non-small cell lung cancer (NSCLC ) patients .In recent years ,epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKIs) represented by Gefitinib ,Erlotinib ,Afatinib and an-aplastic lymphoma kinase (ALK) TKIs represented by Crizotinib have remarkable efficacy .However ,the efficacy for most first-generation EGFR-TKI and ALK-TKI is weakened due to secondary resistance .Currently ,the third-generation EGFR-TKI which successfully against drug resistance is based on research and development of the second-generation .In addition ,there are many other targeted inhibitors of mutation sites for advanced NSCLC .Unfortunately ,the largest proportion of Kirsten rat sar-coma viral oncogene homolog (K-RAS) mutation is not targetable with small molecule inhibitors currently .Therefore ,based on mechanisms exploration of tumor driven gene mutation ,its target drug research and development will be greatly addressed in the future .

  7. Evaluation of pemetrexed in treating advanced non-small cell Lung cancer%培美曲塞二线治疗晚期非小细胞肺癌的临床评价

    Institute of Scientific and Technical Information of China (English)

    盛文奇; 束永前; 沈华; 朱必清; 刘凌翔; 沈洪兵

    2009-01-01

    Objective To investigate the efficacy of pemetrexed as a second line treatment for advanced-stage non-small cell lung cancer (NSCLC), which was failed to the standard platium-based chemotherapies. Methods Fifty qualifed patients received pemetrexed 500 mg/m~2, for 2 cycles with every 21 days each. Quality of life(QOL) was assessed with QLQ-30 and QLQ-LC13 forms. Disease control was assessed by response evaluation criteria in solid tumors(RECIST). Results Of 50 cases, 22 cases had partial remission (PR) , 20 cases had stable disease (SD) , and 8 cases had progressive disease (PD). Except the social function in the 5-function scales, all other 4 functions and the mean scores of QOL were improved significantly after pemetrexed therapy (P<0. 05). Mean scores of major general symptoms, like hypodynamia and anorexia, and disease-related symptoms were decreased significantly (P<0. 05). Conclusion As a second line treatment, premetrexed not only increases the survival, but also reduces tumor-related symptoms and improves QOL in the advanced-stage NSCLC patients, who have received platium-based regiments previously.%目的 探讨培美曲塞二线治疗晚期非小细胞肺癌(NSCLC)的临床疗效.方法 一线含铂方案化疗后复发的晚期NSCLC患者50例,使用培美曲塞(500 mg/m~2,d_1)治疗2个周期(21 d×2).治疗前后分别采用QLQ-C30和QLQ-LC13问卷,对患者的生活质量和症状进行评价,按RECIST标准评判临床疗效.结果 部分缓解(PR)6例,稳定(SD)26例,进展(PD)18例.与治疗前比较,除社会功能外,体格、角色、情感、认知4种功能状态和整体生活质量评分均显著提高(P<0.05);乏力、食欲不振2个全身症状及5种疾病相关症状评分显著降低(P<0.05).结论 培美曲塞二线治疗晚期NSLC能显著改善肺癌相关症状,提高患者生活质量.

  8. Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up

    Institute of Scientific and Technical Information of China (English)

    Yong-song GUAN; Yuan LIU; Qing ZOU; Qing HE; Zi LA; Lin YANG; Ying HU

    2009-01-01

    Objective: In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) injection in patients with advanced non-small-cell lung cancer (NSCLC) in the combination with the therapy of bronchial arterial infusion (BAI). Methods: A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 (the combo group), while the remaining 39 were treated with only BAI (the control group). Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer Institute's Common Toxicity Criteria and response evaluation criteria in solid tumor (RECIST), respectively. Time to progression (TTP) and survival rates were also analyzed by Kaplan-Meier method. Results: In the combo group,19 patients received a total of 49 injections of rAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia (P0.05). Patients in the combo group had a longer TTP than those in the control group (a median 7.75 vs 5.5 months, P=0.018). However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, com-pared with 92.31%, 69.23%, and 38.83% in the control group (P=0.224). Conclusion: Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the quality of life and delayed the disease progression. A further study to better determine the efficacy of this combination therapy is warranted.

  9. 厄洛替尼治疗晚期非小细胞肺癌36例临床观察%Clinical observation of erlotinib in the treatment for 36 patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李麦冬; 吉兆宁

    2013-01-01

    Objective To investigate the curative effect and the side effect of targeted drug of erlotinib in the treatment of patients with advanced non-small cell lung cancer (NSCLC) as the first or second line. Methods 36 patients who with NSCLC at ⅢA or Ⅳ stage were selected in this study, were all confirmed by pathology or cytology. Firstly those patients who were with low physical state were given erlotinib as the first line treatment or at least one to two cycles of chemotherapy when until death or disease progression or intolerable toxici-ty occurred, then they were orally applied with erlotinib as the second line treatment. The curative effect and the adverse reactions were compared between the two groups. Results There was no CR case, 9 PR cases ( 25. 0% ), 17 SD cases ( 45. 2% ), and 10 PD cases ( 27. 8% ). The overall response rate ( ORR ) was 25. 0% , and the disease control rate ( DCR ) was 72. 2% . The median progression-free survival was 5. 3 months. The statistics showed the patients with adenocarcinoma had a significant higher DCR than those with squamous carcinoma ( P = 0. 029 ). The common adverse reactions of erlotinib were rash and diarrhea which could be controlled after treatment. Conclusion Erlotinib has favorable curative effect and slight adverse reactions in the treatment of patients with non-small cell lung cancer.%目的 探讨厄洛替尼单药一线或二线治疗晚期非小细胞肺癌的疗效及不良反应.方法收集36例我科就诊的ⅢB期或者Ⅳ期非小细胞肺癌病例:所有患者均为病理学确诊,患者因体力状态较低一线选择厄洛替尼或至少接受1~2个周期化疗,治疗失败或因毒副反应不能耐受后二线选择口服厄洛替尼,具体用法:150 mg/qd,直至病情进展或者不能耐受副反应.结果 在36例患者中,CR0例,PR 9例(25.0%),SD17例(45.2%),PD10例(27.8%),ORR为25.0%,DCR为72.2%.中位TTP为5.3个月,统计学结果显示:病理学类型与患者的DCR有关(P=0.029),腺癌

  10. New First-line Treatment Drug for Advanced Non-small Cell Lung Cancer-Afatinib%晚期非小细胞肺癌一线治疗新药阿法替尼

    Institute of Scientific and Technical Information of China (English)

    安富荣; 王淑萍; 归小龙

    2015-01-01

    阿法替尼是一种口服给药的酪氨酸激酶ErbB家族不可逆抑制药。两项随机、开放标签、多中心Ⅲ期临床试验结果表明,与培美曲塞+顺铂(LUX-Lung 3)或吉西他滨+顺铂(LUX-Lung 6)化疗相比,阿法替尼可显著延长EGFR突变的晚期非小细胞肺癌患者的无进展生存期,患者报告的咳嗽和呼吸困难症状以及健康相关生活质量也优于化疗组。阿法替尼于2013年7月获得美国FDA批准上市,一线治疗伴EGFR外显子19缺失或外显子21替代突变的晚期非小细胞肺癌。本文对阿法替尼的作用机制、药动学特性、临床研究进展以及安全性等作一综述。%Afatinib is an irreversible inhibitor for the ErbB family of tyrosine kinases with oral administration. In two randomized, open-label and multinational phase III trials, the progression-free survival was significantly prolonged by afatinib compared with peme-trexed plus cisplatin (LUX-Lung 3) or gemcitabine plus cisplatin (LUX-Lung 6) in the treatment-naive patients with advanced non-small cell lung cancer ( NSCLC) with activating EGFR mutations. The patient-reported symptoms such as cough and dyspnoea, and certain health-related quality of life after the treatment by afatinib were also better than those treated by control dugs. Afatinib was ap-proved by FDA in July 2013 as the first-line treatment drug for the patients with metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) mutations. The action mechanisms, pharmacokinetics, clinical trials and adverse events were reviewed in this paper.

  11. Randomized Phase II trial of paclitaxel and carboplatin followed by gemcitabine switch-maintenance therapy versus gemcitabine and carboplatin followed by gemcitabine continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Minami Seigo

    2013-01-01

    Full Text Available Abstract Background In recent years, maintenance chemotherapy is increasingly being recognized as a new treatment strategy to improve the outcome of advanced non-small cell lung cancer (NSCLC. However, the optimal maintenance strategy is still controversial. Gemcitabine is a promising candidate for single-agent maintenance therapy because of little toxicity and good tolerability. We have conducted a randomized phase II study to evaluate the validity of single-agent maintenance chemotherapy of gemcitabine and to compare continuation- and switch-maintenance. Methods Chemonaïve patients with stage IIIB/IV NSCLC were randomly assigned 1:1 to either arm A or B. Patients received paclitaxel (200 mg/m2, day 1 plus carboplatin (AUC 6 mg/mL/min, day 1 every 3 weeks in arm A, or gemcitabine (1000 mg/m2, days 1 and 8 plus carboplatin (AUC 5 mg/mL/min, day1 every 3 weeks in arm B. Non-progressive patients following 3 cycles of induction chemotherapy received maintenance gemcitabine (1000 mg/m2, days 1 and 8 every 3 weeks. (Trial registration: UMIN000008252 Results The study was stopped because of delayed accrual at interim analysis. Of the randomly assigned 50 patients, 49 except for one in arm B were evaluable. Median progression-free survival (PFS was 4.6 months for arm A vs. 3.5 months for arm B (HR = 1.03; 95% CI, 0.45–2.27; p = 0.95 and median overall survival (OS was 15.0 months for arm A vs. 14.8 months for arm B (HR = 0.79; 95% CI, 0.40–1.51; p = 0.60, showing no difference between the two arms. The response rate, disease control rate, and the transit rate to maintenance phase were 36.0% (9/25, 64.0% (16/25, and 48% (12/25 for arm A vs. 16.7% (4/24, 50.0% (12/24, and 33% (8/24 for arm B, which were also statistically similar between the two arms (p = 0.13, p = 0.32, and p = 0.30, respectively. Both induction regimens were tolerable, except that more patients experienced peripheral neuropathy in arm A. Toxicities during

  12. Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non-Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

    Energy Technology Data Exchange (ETDEWEB)

    Machtay, Mitchell, E-mail: Mitchell.machtay@uhhospitals.org [University Hospitals/Case Western Reserve University, Cleveland, OH (United States); Bae, Kyounghwa [Radiation Therapy Oncology Group (RTOG) Department of Statistics, Philadelphia, PA (United States); Movsas, Benjamin [Henry Ford Hospital, Detroit, MI (United States); Paulus, Rebecca [Radiation Therapy Oncology Group (RTOG) Department of Statistics, Philadelphia, PA (United States); Gore, Elizabeth M. [Medical College of Wisconsin, Milwaukee, WI (United States); Komaki, Ritsuko [M.D. Anderson Cancer Center, Houston, TX (United States); Albain, Kathy [Loyola University Chicago Stritch School of Medicine, Maywood, IL (United States); Sause, William T. [LDS Hospital, Salt Lake City, UT (United States); Curran, Walter J. [Emory University, Atlanta, GA (United States)

    2012-01-01

    Purpose: Patients treated with chemoradiotherapy for locally advanced non-small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray's proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control

  13. Sequential (gemcitabine/vinorelbine and concurrent (gemcitabine radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

    Directory of Open Access Journals (Sweden)

    Stanzel Sven

    2007-06-01

    Full Text Available Abstract Background The aim of the study was to determine the maximal tolerated dose (MTD of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC and to evaluate the efficacy of this regime in a phase II study. Methods 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2 and vinorelbine (30 mg/m2 at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized. Results MTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3 esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg, representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT grade 3 was reached. In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months. The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7] months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6] months. Conclusion

  14. 晚期非小细胞肺癌的药物治疗进展%New progress of drug therapy in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    胡毅; 陶海涛

    2014-01-01

    肺癌目前仍是死亡率较高的恶性肿瘤。近年来随着分子靶向治疗的进展,非小细胞肺癌的治疗已经取得了长足的进步。许多转化性临床研究结果带来近期疗效、生活质量尤其是生存的显著提高。传统的化疗是非小细胞肺癌治疗的基石,是野生型以及突变未知患者治疗的首选;分子靶向治疗则为敏感突变的患者带来了革命性的转变,是目前治疗的中流砥柱;而免疫治疗在免疫检查点抑制剂上的突破也结束了长期混沌的状态,成为非小细胞肺癌治疗的新兴力量。而无论是化疗、靶向治疗还是免疫治疗,基于肿瘤分子病理改变的精确治疗是目前非小细胞肺癌治疗发展的趋势。%[ABSTRACT]Lung cancer is the leading cause of cancer mortality. Due to the progress in molecular target therapy, great progress has been achieved in advanced non-small cell lung cancer (NSCLC). Many treatments have been demonstrated to improve the objective remission rate, quality of life and even the progressive free survival and overall survival in translational researches. Traditional chemotherapy is very important for NSCLC patients, especially for those wild-type or unknown gene mutation patients;the progress in molecular target therapy just revolutionize the treatment of NSCLC and become the ifrst choice for those patients with gene sensitive mutation; the progresses of drugs which target speciifc checkpoint of immune system have led the immunotherapy to new heights, immunotherapy become the new choice for NSCLC. No matter chemotherapy, target therapy or immunotherapy, the treatments based on exact change of the molecular pathogenesis are the development direction of NSCLC.

  15. A Randomized Phase I/II Trial to Compare Weekly Usage with Triple Weekly Usage of Paclitaxel in Concurrent Radiochemotherapy for Patients with Locally Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Anhui SHI

    2011-03-01

    Full Text Available Background and objective Although the guidelines of the National Comprehensive Cancer Network of USA recommend that the standard therapy for locally advanced non-small cell lung cancer (LANSCLC is concurrent chemoradiotherapy. There is ongoing controversy about the treatment regimen which combines chemotherapy concurrently with radiotherapy. The aim of this study is to compare weekly usage with triple weekly usage of paclitaxel in concurrent radiochemotherapy for patients with LANSCLC, and to obtain the best paclitaxel regimen in the concurrent radiochemotherapy. Methods From April 2006 to April 2009, some LANSCLC patients in multicenter were randomly divided into weekly usage (45 mg/m2, 1 times/week, a total of 270 mg/m2 in six weeks and triple weekly usage (15 mg/m2, 3 times/week, a total of 270 mg/m2 in six weeks group of paclitaxel by a random number table. All patients were treated with 3D radiotherapy, and 95% planning target volume (PTV received a prescription dose of (60-70 Gy/(30-35times/(6-7weeks, (1.8-2.0 Gy/fraction. Then the side effects, response and overall survival rate were compared between two groups of patients. Results Thirty-eight LANSCLC patients were enrolled. Weekly usage and triple weekly usage group were 20 and 18 patients, respectively. In the triple weekly usage group, the side effects were 12 patients had radiation esophagitis of I-II degree, 1 patient had radiation esophagitis of III degree, 2 patients had radiation pneumonitis of I degree, 1 patient had radiation pneumonitis of II degree, 1 patient had radiation pneumonitis of III degree and died of respiratory failure, 2 patients developed weight loss of I degree. In the weekly usage group, the side effects were 11 patients had radiation esophagitis of I-III degree, 6 patients had radiation pneumonitis of II-III degree, 2 patients developed weight loss of I degree, 6 patients developed leucopenia of III-IV degree. The response rate of two groups was 88.8% and 50

  16. 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

    2014-01-01

    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. Patie

  17. 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 wit

  18. Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shanshan Chen; Shun Lu 

    2015-01-01

    As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-smal cel lung cancer (NSCLC) and has proven ef ective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in com-bination with first-line chemotherapy for non-squamous NSCLC. Smal-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not al other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

  19. Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer:a systematic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Zhong-liang Liu; Wei-rong Zhu; Wen-chao Zhou; Hai-feng Ying; Lan Zheng; Yuan-biao Guo; Jing-xian Chen; Xiao-heng Shen

    2014-01-01

    BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs (TCMHs) may increase efifcacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted. OBJECTIVE:This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC. SEARCH STRATEGY:PubMed, the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web site of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were searched; the search included all documents published in English or Chinese before October 2013. INCLUSION CRITERIA:We selected randomized controlled trials based on speciifc criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC. DATA EXTRACTION AND ANALYSIS: The modiifed Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate (ORR; complete response + partial response divided by the total number of patients), disease control rate (DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    Schimek-Jasch, Tanja; Prokic, Vesna; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); German Cancer Consortium (DKTK) partner site: Freiburg, Heidelberg (Germany); Troost, Esther G.C. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Ruecker, Gerta [University Medical Center Freiburg, Institute for Medical Biometry and Statistics, Centre for Medical Biometry and Medical Informatics, Freiburg (Germany); Avlar, Melanie [German Cancer Research Center (DKFZ), Heidelberg (Germany); Duncker-Rohr, Viola [Ortenau-Klinikum Offenburg-Gengenbach, Department of Radiation Oncology, Gengenbach (Germany); Mix, Michael [University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); German Cancer Consortium (DKTK) partner site: Freiburg, Heidelberg (Germany)

    2015-02-10

    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

  1. Guiding individualized therapy in advanced non-small cell lung cancer by detection of Survivin protein%检测Survivin蛋白指导NSCLC的个体化治疗

    Institute of Scientific and Technical Information of China (English)

    朱建荣; 郁震; 万小蔹; 崔小川

    2015-01-01

    目的 探讨根据肿瘤组织中Survivin蛋白的表达情况指导非小细胞肺癌(NSCLC)进行个体化治疗的作用和意义.方法 117例确诊为NSCLC的患者按2∶1比例随机分2组.个体化治疗组(n=78)根据组织标本中Survivin蛋白的表达情况,选择个体化方案化疗,Survivin蛋白阳性患者采用非铂化疗方案,Survivin蛋白阴性患者采用含铂类药物化疗方案;标准治疗组(n=39)选择含铂类药物的一线标准方案化疗.比较2个治疗组的化疗效果,以Kaplan-Meier法分析2个治疗组患者生存期的差异.结果 NSCLC患者中Survivin蛋白表达的阳性率为51.3%;个体化治疗组和标准治疗组的化疗有效率分别为55.1%和33.3%(x2=4.949,P=0.026),两组的平均生存期分别为13.7个月和10.8个月,个体化治疗组的疗效明显优于标准治疗组(P =0.009).结论 检测Survivin蛋白以指导NSCLC患者进行个体化治疗可以提高化疗效果,并延长生存时间.%Objective To investigate the value of detecting Survivin protein in biopsy specimens of advanced non-small cell lung cancer (NSCLC) patients for individualized therapy.Methods 117 pathologically proven NSCLC patients were enrolled and randomly assigned in 2 ∶ 1 ratio to either the individualized treatment group or the standard treatment group.In individualized treatment group,platinum-based chemotherapy was given to Survivin protein negative patients,chemotherapy without platinum was given to Survivin protein positive patients after Survivin assessment.The standard treatment group received first-line platinum-based chemotherapy regimen.Differences in treatment effect between the groups were statistically analyzed.Survival differences were analyzed by Kaplan-Meier survival curves.Results The expression of Survivin protein was 51.3% among 78 cases.There was statistical significance in outcome between the individualized treatment group and the standard treatment group (response rate:55.1% vs 33.3

  2. Efficacy and safety of Afatinib in patients with advanced non-small cell lung cancer%阿法替尼治疗晚期非小细胞肺癌的疗效和安全性观察

    Institute of Scientific and Technical Information of China (English)

    张丽; 汤依群; 史美祺; 夏国豪; 王丽; 寇莹莹; 马祥垒

    2015-01-01

    Objective To observe the clinical efficacy and safety of afatinib,a second generation epidermal growth factor receptor tyro-sine kinase inhibitor (EGFR-TKIs),in the treatment of patients with advanced non-small cell lung cancer (NSCLC).Methods A to-tal of 37 patients with advanced NSCLC diagnosed pathologically were enrolled into the study.Ten patients with EGFR mutations were first-line treated with oral afatinib 40 mg·d -1 until disease progression.Two squamous carcinoma patients were second-line treated with 40 mg·d -1 of afatinib,and others with 50 mg·d -1 for second-line and beyond treatment.The short-term efficacy,progression free sur-vival (PFS)and adverse events were observed.Results Among the 37 patients,there was no case with complete response;14 cases (37.8%)had partial response,19 cases (51.4%)had stable disease and 4 case (10.8%)had progressive disease;the objective re-sponse rate (ORR)was 37.8% and the disease control rate (DCR)was 89.2%;the median progression free survival (PFS)was 6.9 months (95%CI 3.8 ~10.0).Further sub group analysis showed that the first-line treated subjects with EGFR mutations (ORR 100%,PFS 12.1 months)were more effective than that second-line and beyond treatment with unknown EGFR mutations (ORR 14.8%,PFS 5.3 months)with statistically significant difference (P ﹤ 0.01 ).The most common adverse events were diarrhea (100.0%)and rash (83.8%).Conclusions Afatinib is effective and safe as fist-line treatment for patients with EGFR mutations advanced NSCLC.%目的:观察第二代表皮生长因子受体酪氨酸激酶抑制剂(EGFR -TKIs)阿法替尼治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法纳入37例经病理学或细胞学确诊的Ⅳ期非小细胞肺癌(NSCLC)患者。一线表皮生长因子受体(EGFR)突变患者10例,给予阿法替尼每日40 mg 口服;二线及以上患者27例,其中2例二线鳞癌患者给予阿法替尼每日40 mg 口服,其余

  3. 77 FR 24717 - Scientific Information Request on Local Therapies for the Treatment of Stage I Non-Small Cell...

    Science.gov (United States)

    2012-04-25

    ... Therapies for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to... for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to Advanced... effectiveness review of the evidence for local therapies for the treatment of stage I non-small cell lung...

  4. Research Advances of the Relationship between Vascular Endothelial Growth Factor and Non-small Cell Lung Cancer%血管内皮生长因子与非小细胞肺癌关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    李高峰; 段林灿; 陈明清

    2004-01-01

    血管内皮生长因子(vascular endothelial growth factor,VEGF)是作用最强、特异性最高的血管生成调控因子.非小细胞肺癌(non-small cell lung carcinoma.,NSCLC)易于早期转移的生物学特性与VEGF的作用相关.就VEGF与NSCLC的发生、发展、预后关系和作为治疗靶点的价值研究领域的最新进展进行综述.

  5. 肿瘤标志物与非小细胞肺癌脑转移的相关性%Relationship between serum tumor markers and brain metastasis in patients with ad-vanced non - small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘艳萍; 曾爱屏; 宋向群; 周韶璋; 于起涛

    2015-01-01

    Objective:To explore the relationship between serum tumor markers and brain metastasis in patients with advanced non - small cell lung cancer(NSCLC). Methods:The clinical data of 289 advanced NSCLC patients hospitalized from April 2009 to October 2013 were retrospectively analyzed. All the enrolled patients were newly diag-nosed NSCLC with stage Ⅳ and not received treatment previously. Of those patients,223 had no brain metastasis. The rest were diagnosed with brain metastasis. Results:The incidence of brain metastasis was 22. 8%(66 / 289),the medi-an survival time of patients with the brain metastasis was 9. 4 months. The 1 - year and 2 - year survival rates were 37% and 15% respectively. The serum level of carcinoembryonic antigen(CEA)was significantly different between no brain metastasis patients and those who had(P = 0. 001). The median value of CEA of patients with and without brain metastasis was 6. 8ng/ ml,16. 0ng/ ml respectively. Overall survival was significantly shorter among patients with elevated serum CEA(median survival 15 months vs. 8 months,P = 0. 027)or CA125(median survival 13 months vs. 7 months,P = 0. 008). In multivariate analysis,CA125,radiotherapy and sex were independent prognostic factors for brain metastasis(P < 0. 05). Conclusion:The high serum CEA level may be potentially used as an indicator to predict the probability of brain metastasis in patients with NSCLC. The high serum CA125 may be used as reference index of the prognosis of brain metastasis in patients with NSCLC.%目的:探讨血清 CEA、CA125、CA153、CA199、CA724和 CYFRA21-1水平与晚期非小细胞肺癌(NSCLC)脑转移发生和预后的相关性。方法:回顾性分析我院2009年4月至2013年10月289例(非脑转移223例,脑转移66例)未进行过任何治疗的Ⅳ期 NSCLC 患者临床资料。结果:全组病例脑转移发生率为22.8%(66/289),66例脑转移的中位生存期为9.4个月,1年、2年生存率分别为37%、15

  6. 非小细胞肺癌吉西他滨药物耐药相关基因研究进展%Advances of Drug Resistance Marker of Gemcitabine for Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    陈莹; 钱晓萍; 刘宝瑞

    2011-01-01

    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.%随着药物基因组学、药物遗传学的发展,基因指导下个体化治疗成为提高非小细胞肺癌(non-small cell lung cancer,NSCLC)化疗疗效的有效途径之一.确定药物的相关预测性分子标志物从而指导临床治疗、提高疗效被广泛关注.吉西他滨是目前NSCLC常用化疗药物之一,本文主要阐述了近年来吉西他滨药物耐药相关基因在NSCLC个体化治疗方面的研究进展.

  7. Advances of Driver Gene and Targeted Therapy of Non-small Cell Lung Cancer%非小细胞肺癌驱动基因突变及靶向治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    张丹(综述); 黄艳; 王红阳(审校)

    2014-01-01

    肺癌是癌症死亡的重要原因。驱动基因的发现使肿瘤治疗不再“一刀切”。靶向治疗改变了癌症药物治疗的现状成为“带眼睛的子弹”,其疗效可见并为肺癌治疗带来一场革命。驱动基因及靶向治疗已经成为非小细胞肺癌(non-small cell lung cancer, NSCLC)新的代名词。2013年中国美国临床肿瘤学会(American Society of Clinical Oncology, ASCO)年会发布了关于NSCLC的11种驱动基因突变频率,本文将就此11种NSCLC驱动基因突变的结构、功能及靶向药物治疗进行阐述。%Lung cancer is the leading cause of cancer-related mortality in the worldwide. hTe discovery of drive gene makes tumor treatment is no longer"one-size-ifts-all". Targeted therapy to change the present situation of cancer drugs become"bullet"with eyes, the effect is visible and bring a revolution in the treatment of lung cancer. hTe diver gene and tar-geted therapy have became the new cedule of non-small cell lung cancer (NSCLC). Society of Clinical Oncology (ASCO) has showed 11 kinds of diver genes. Here, we review the functional and structural characteristics and the targeted therapy in the 11 kinds of driver gene mutations.

  8. 凝血功能与非小细胞肺癌相关机制研究进展%Advances on Mechanisms of Coagulation with Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    李艳华(综述); 魏素菊(审校)

    2013-01-01

    Recently, researchers have been increasingly finding coagulation disorders are commonly the first sign of malignancy. It has now been established that cancer development leads to an increased risk of thrombosis, and conversely, excessive activation of blood coagulation profoundly influences cancer progression. In patients with lung cancer, a sustained stimulation of blood coagulation takes place. Cancer cells trigger coagulation through expression of tissue factor, and affect coagulation through expression of thrombin, release of microparticles that augment coagulation and so on. Coagulation also facilitates tumour progression through release of platelet granule contents, inhibition of natural killer cells and recruitment of macrophages. Non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung malignancies. In the present review, we summarized the newly updated data about the physiopathological mechanisms of various components of the clotting system in different stages of carcinogenesis in NSCLC.%近来研究越来越多地发现凝血功能紊乱通常是恶性肿瘤的首发迹象。现在已经证实,肿瘤导致血栓形成的风险增加,而凝血功能的过度激活也极大地影响肿瘤的进展。在肺癌患者中,存在着持续的凝血刺激。癌细胞通过组织因子(tissue factor, TF)的表达激活凝血功能;通过凝血酶的表达和促凝血微粒的释放等影响凝血功能。凝血功能也通过介导血小板释放其颗粒内容物、抑制自然杀伤细胞和募集巨噬细胞而促进肿瘤的进展。非小细胞肺癌(non-small cell lung cancer, NSCLC)占肺癌的80%-85%,本文就凝血系统各个组分在NSCLC发生发展中的病理生理学机制的最新研究进展进行综述。

  9. The Question and Analysis about Maintenance Therapy in Advanced Non-small Cell Lung Cancer%晚期NSCLC维持治疗质疑与问题解析

    Institute of Scientific and Technical Information of China (English)

    刘晓晴

    2014-01-01

    Recently, several studies have been carried about maintenance therapy in non-small cell lung cancer, and some chemotherapy agents have been approved for clinical practice. But there are still a lot of questions about maintenance therapy that we have to consider. For example, the defects of design in maintenance therapy trials;how to choose gold standard of maintenance therapy for evaluation;who beneift from the maintenance therapy and how to estimate pharmaceutical eco-nomics. In this paper, we will make deep analysis about these issues.%近年来,针对晚期非小细胞肺癌的维持治疗进行了诸多临床研究,而这些研究亦已使得部分药物通过审批应用于临床实践。但是目前维持治疗仍存在诸多不容忽视的问题和质疑,如维持治疗试验设计中存在的缺陷和疏漏;维持治疗评价金标准是什么;获益人群以及维持治疗的药效经济学等问题,本文就上述问题作进一步解析。

  10. SUCCESSFUL REGISTRATION OF DOMESTIC BIOANALOGUE OF BEVACIZUMAB – NEW OPPORTUNITIES FOR EFFECTIVE TREA TMENT OF PATIENTS WITH NON-SQUAMOUS CELL NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    S. V. Orlov

    2015-01-01

    Full Text Available Comparison of the efficacy and safety of drugs "Avegra®" and "Avastin®" used in combination with paclitaxel and carboplatin as first-line therapy in patients with locally inoperable or metastatic NSCLC. The study included 138 patients, male and female aged 18 to 75 years with newly diagnosed inoperable or widespread metastatic NSCLC (except squamous cell NSCLC, relevant eligibility criteria. After passing screening, patients were centrally randomized in one of the study groups in a 1:1 ratio. Treatment was carried out according to the following scheme: "Avegra®" or "Avastin®", 15 mg/kg intravenously over 90 minutes immediately after carboplatin on day 1 of each 3‑week cycle + paclitaxel 175 mg/m² intravenously over 3 hours on day 1 of each 3‑week cycle + carboplatin dose required to achieve AUC 6 mg/ml×min, intravenously over 15–30 minutes, immediately following paclitaxel, on the first day of each three-week cycle. The treatment lasted for six cycles of three weeks or until progression or until the development of intolerable toxic effects. Based on CT scan assessment performed by an independent specialist, the overall response rate (ORR, partial response rate + complete response rate defined as a primary endpoint was 42.59% (95% CI 30.33–55.83% in "Avegra®" arm and 39.29% (95% CI 27.58–52.27% in "Avastin®" arm, respectively. The difference in ORR between study drug and comparator was 3.30% with 95% CI –14.96–21.40% (р =0.874, the Pearson x² test with Yates correction. The lower limit of calculated 95% CI (-14.96% exceeds the specified non-inferiority margin and it is indicating the non-inferiority of "Avegra®" efficacy compared to "Avastin®". During the study period the incidence of adverse events, including severe adverse events (grade 3–4 according to CTCAE related with the investigational drugs, did not have statistically significant differences in both study arms.The drug "Avegra®" in direct comparison to "Avastin®" demonstrated equal efficacy, similar safety and immunogenicity profile, equal pharmacokinetic characteristics. Based on the results of the clinical study the first biosimilar of bevacizumab — drug "Avegra®" was successfully registered in Russian Federation in November 2015 and can be recommended for use in clinical practice.

  11. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial

    DEFF Research Database (Denmark)

    Kim, E.S.; Hirsh, V.; Mok, T.;

    2008-01-01

    BACKGROUND: Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy. We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer wh...

  12. 非小细胞肺癌EML4-ALK融合基因检测技术研究进展%Advances in assay of EML4-ALK gene rearrangements in non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    陈健; 李治桦; 刘晓晴

    2014-01-01

    Echinoderm microtubule associated protein like 4-anaplastic lymphomakinase ( EML4-ALK) rearrangement is another driver-mutation in non-small-cell lung cancer (NSCLC) besides epidermal growth factor receptor (EGFR).Accu-rate identification of EML 4-ALK lung adenocarcinoma is essential for the selection of appropriate therapy .Immunohisto-chemistry (IHC), fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR) are the main three assay methods for clinical practice .Recently, researchers have done lots of work on the exploration of detection , diagnosis, and treatment prediction of carcinoma based on serum proteomics .In this paper, recent developments in these fields are reviewed.%棘皮动物微管相关蛋白4-间变性淋巴瘤激酶( echinoderm microtubule associated protein like 4-anaplastic lymphomakinase, EML4-ALK)融合基因是继表皮生长因子受体(epidermal growth factor receptor ,EGFR)之后的又一非小细胞肺癌驱动基因。 EML4-ALK基因检测对临床治疗至关重要。目前,EML4-ALK基因的检测方法包括免疫组化、免疫荧光原位杂交、基于PCR扩增方法等。近年来,国内外学者对血清蛋白质组学在肿瘤检测、诊断、疗效预测方面做了大量有益的探索。该文综述了EML4-ALK的检测方法以及ALK血清蛋白质组学等方面的研究进展。

  13. Translational research on crizotinib in EML4-ALK positive advanced non-small cell lung cancer%Crizotinib治疗EML4-ALK阳性晚期非小细胞肺癌的临床转化研究

    Institute of Scientific and Technical Information of China (English)

    李嘉瑜; 李雪飞; 周彩存

    2012-01-01

    棘皮动物微管相关蛋白样4(echinoderm microtubule associated protein like 4,EMLA)间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因(EML4-ALK)是近年来新发现的癌变驱动基因,该融合基因阳性的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者有其独特的临床特征,可能与表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)耐药相关.针对EML4-ALK基因突变的新靶向药物-ALK抑制剂crizotinib,现已经进入Ⅲ期临床试验.Ⅰ期及Ⅱ期临床试验均证实,crizotinib治疗EML4-ALK阳性晚期NSCLC患者有效,能够改善肿瘤患者症状,患者的无进展生存期(progression free survival,PFS)延长,总体有效率(overall response rate,ORR)提高.且crizotinib的毒性作用较小,与传统化疗相比,患者耐受性较好.与其他TKI一样,crizotinib也存在获得性耐药现象,其耐药机制有待进一步研究.本文就crizotinib从基础研究向治疗EML4-ALK阳性晚期NSCLC患者临床应用的转化过程作一回顾.

  14. 晚期非小细胞肺癌中EGFR基因突变及靶向药物治疗临床分析%EGFR Gene Mutation and Targeted Therapy of Advanced Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    袁惠芳

    2015-01-01

    目的:探讨晚期非小细胞肺癌中EGFR基因突变及靶向药物治疗的临床疗效分析;方法对34例病例采用xTAG液相芯片技术进行基因检测,其中EGFR基因突变11例,其中EGFR E19基因突变6例,EGFR E21基因突变3例,EGFR E20/2基因突变2例,未检测到突变15例,对EGFRE19/21基因突变的9例患者采用吉非替尼250mg/天,口服,持续口服至进展;结果3例完全缓解,2例部分缓解,1例疾病进展,3例疾病稳定;结论EGFR基因突变患者应用靶向药物治疗可明显改善生活质量、提高疾病控制率与生存率。%Objective To investigate the clinical efficacy of targeted therapy and EGFR gene mutation in non-small cell lung cancer. Methods Gene detection by xTAG liquid chip technology was conducted in 34 cases. Among 11 cases of EGFR gene mutation, there were 6 E19 mutation, 3 E21 mutation, and 2 E20/2 mutation. Nine cases with E19/21 mutation were treated with gefitinib 250mg/day orally. Results Three cases were completely remitted, 2 cases partial remitted, 1 with disease progression, and 3 cases stabilized. Conclusion Targeted therapy can significantly improve the quality of life and survival rate of patients with EGFR gene mutation.

  15. Advance in clinical research of non-small cell lung cancer vaccines%非小细胞肺癌疫苗治疗的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    杨露璐; 吴一龙

    2012-01-01

    The therapeutic cancer vaccines have low toxicity and well tolerance. However, many clinical studies of vaccines for NSCLC have not made significant progress. The major difficulties in the development of therapeutic cancer vaccines include the lack of tumor specific antigen, the tumor escape mechanisms from host immune surveillance and immune tolerance. In recent years, new insights in the interaction between tumors and the immune system, the better identification of antigenic targets, the addition of immunoadjuvants and the production of more efficient delivery systems have resulted in more sophisticated vaccines, such as antigen-specific vaccines targeting melanoma-associated antigen-A3 , mucin 1 and EGF, and whole-cell vaccines such as belagenpumatucel-L. These vaccines have shown promising results in phase II clinical trials, and need to be evaluated in Phase II clinical trials.%非小细胞肺癌(non-small cell lung cancer,NSCLC)的疫苗治疗具有不良反应小、耐受性好的特点,但众多的临床研究并未取得突破性的进展.影响疫苗治疗肺癌的主要困难包括由于肿瘤免疫原性弱而缺乏肿瘤特异性抗原以及宿主免疫监视下的肿瘤免疫逃逸和免疫耐受.近几年来,随着人们对肿瘤和免疫系统关系的进一步认识,特异性肿瘤抗原的发现及免疫佐剂和载体的发展,疫苗治疗NSCLC已经取得了显著的进展,如melanoma-associated antigen-A3疫苗、针对mucin 1抗原的疫苗、EGF疫苗等抗原特异性疫苗以及将TGF-β2转染NSCLC细胞株制成的全细胞疫苗Belagenpumatucel-L等.多个Ⅱ期临床研究已经证实了它们在NSCLC中的疗效,相应多中心的Ⅲ期临床研究正在进行中.

  16. 非小细胞肺癌细胞学标本EGFR检测的研究进展%Research advancement on EGFR mutation detection in cytological samples of non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    陈桂阳; 荣福; 刘静

    2013-01-01

    The main therapies of non-small cell lung cancer (NSCLC) are surgery,chemotherapy,radiotherapy and targeted therapy.With development of targeted therapy,it is found that tyrosine kinase inhibitor is effective for patients with epidermal growth factor receptor (EGFR) mutations.Screening of such drugs before treatment is a premise of individualized treatment,and genetic testing of tissue samples is currently gold standard.In most cases,the diagnosis of lung cancer is performaed on cytological specimens,therefore,there is a need to obtain a complete and reliable molecular diagnosis on cytological specimens.In recent years,EGFR mutation detection in cytological samples of NSCLC has become a trend,and major cytogenetic specimen types include peripheral blood,pleural effusion and fine needle aspiration.This review aims to present an overview of the current knowledge of the use of cytological specimens for the evaluation of EGFR gene states in NSCLC.%非小细胞肺癌治疗手段以手术、化疗、放疗和靶向治疗为主.随着靶向治疗研究的进展,发现表皮生长因子受体(EGFR)突变患者接受小分子酪氨酸激酶抑制剂靶向治疗效果佳.进行这类药物治疗前的筛选是个体化治疗的前提,目前以组织标本基因检测为金标准.但是进展期患者的病理诊断很多时候是根据细胞学标本,部分细胞学标本是惟一的标本来源.近年来肺癌细胞学标本行EGFR检测已经成为一种趋势,主要细胞学标本类型包括外周血、胸腔积液及细针穿刺标本.本文旨在对目前使用细胞学标本评价非小细胞肺癌EGFR基因状态方面做一个概述.

  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. EGFR基因多态性对EGFR-TKIs治疗晚期NSCLC疗效和预后的影响%Effects of EGFR Gene Polymorphisms on Efficacy and Prognosis in Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs

    Institute of Scientific and Technical Information of China (English)

    笪良山

    2013-01-01

    An increasing number of patients with advanced non-small cell lung cancer (NSCLC) have been treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, significant differences in response to EGFR-TKIs have been shown among advanced NSCLC patients. Recently, selection of patients was mainly based on EGFR gene mutation detection. Nevertheless, mutation detection is often limited by tumour tissues derivation, technique complexity, high cost, and so on. It is urgent to seek other biological markers to predict efficacy of EGFR-TKIs. Many studies have founded that the EGFR gene polymorphisms are also associated with clinical outcome and prognosis in treatment of advanced NSCLC with EGFR-TKIs. Here, we presented a review discussing the correlation between EGFR gene polymorphisms and the efficacy of EGFR-TKIs in advanced NSCLC.%表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFRTKIs)在晚期非小细胞肺癌患者(non-small cell lung cancer,NSCLC)中的应用越来越广泛,但患者的疗效存在明显差异.目前主要是根据EGFR基因突变来选择患者,然而,其检测常受到肿瘤组织来源困难、技术复杂、费用高等因素限制.因此,临床亟待寻求其他生物学标记物来预测EGFR-TKIs疗效.近来有诸多研究发现EGFR基因多态性与晚期NSCLC患者EGFR-TKIs疗效及预后也存在相关性,现将其研究进展作一综述.

  19. Cetuximab in non-small-cell lung cancer.

    Science.gov (United States)

    Carillio, Guido; Montanino, Agnese; Costanzo, Raffaele; Sandomenico, Claudia; Piccirillo, Maria Carmela; Di Maio, Massimo; Daniele, Gennaro; Giordano, Pasqualina; Bryce, Jane; Normanno, Nicola; Rocco, Gaetano; Perrone, Francesco; Morabito, Alessandro

    2012-02-01

    Cetuximab is a chimeric human-mouse anti-EGF receptor monoclonal antibody. In Phase I studies, no dose-limiting toxicities were observed with cetuximab as a single agent or combined with chemotherapy; pharmacokinetic and pharmacodynamic analyses supported 250 mg/m(2) weekly administration. Skin toxicity, diarrhea and fatigue were the most common toxicities. The positive results obtained in Phase II trials in patients with advanced non-small-cell lung cancer prompted two randomized Phase III trials evaluating cetuximab in addition to first-line chemotherapy. Both trials showed a small benefit in overall survival for the experimental treatment, which was considered insufficient by the EMA for marketing approval. However, a subgroup analysis of the FLEX Phase III trial recently demonstrated a larger survival benefit from the experimental treatment in patients with high immunohistochemical EGF receptor expression. This finding, if confirmed prospectively, could represent a new opportunity for positioning cetuximab into the standard treatment of advanced non-small-cell lung carcinoma.

  20. [Intercalated Combination of Chemotherapy and EGFR-TKIs versus Chemotherapy Alone in the First-line Treatment of Advanced Non-small Cell Lung Cancer: A Meta-analysis].

    Science.gov (United States)

    Hong, Chaoyu; Mei, Tonghua; Wang, Jin

    2016-12-20

    背景与目的 化疗与表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors, EGFR-TKIs)联合疗法一直是许多研究的焦点,其中间插联合疗法受到了更多研究者的关注。本研究旨在系统评价化疗与EGFR-TKIs间插联合疗法对比单独化疗一线治疗晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的有效性及安全性。方法 检索The Cochrane Library、PubMed、EMBASE、中国生物医学文献数据库(CBM)、知网和万方等数据库关于化疗间插联合EGFR-TKIs疗法和单独化疗一线治疗晚期NSCLC的随机对照试验(randomized controlled trial, RCT),分析如下结局指标:无进展生存期(progression-free survival, PFS)、总体生存期(overall survival, OS)、客观缓解率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)以及不良反应发生率。由两名研究者根据Cochrane系统评价手册筛选文献、进行质量评价以及提取并交叉核对数据。应用Stata12.0软件进行meta分析。结果 本研究共纳入6个RCT,共计933例晚期NSCLC患者。Meta分析结果表明,在晚期NSCLC患者一线治疗中,与单独化疗相比,间插联合疗法虽然延长了患者的PFS(HR=0.72, 95%CI: 0.53-0.98, P=0.037),但并不能提高其OS(HR=0.85, 95%CI: 0.72-1.01, P=0.060)、ORR(OR=1.59, 95%CI: 0.86-2.95, P=0.142)和DCR(OR=1.09, 95%CI: 0.95-1.25, P=0.226)。进一步的亚组分析发现,间插联合疗法提高了女性、腺癌、从不吸烟和EGFR突变等患者的PFS,差异具有统计学意义。在安全性方面,间插联合疗法的主要不良反应为皮疹(OR=7.81, 95%CI: 3.74-16.34, P<0.001)和腹泻(OR=2.73, 95%CI: 1.92-3.89, P<0.001)。结论 一线接受化疗间插联合EGFR-TKIs治疗的NSCLC患者的PFS明显高于接受单独化疗者,其主要不良事件是皮疹和腹泻。因此,间插联

  1. 两种不同给药方式对晚期非小细胞肺癌紫杉醇脂质体化疗的影响%EFFECTS OF DIFFERENT DELIVERY WAYS OF PACLITAXEL LIPOSOME ON THE CHEMOTHERAPY FOR ADVANCED NON SMALL CELL LUNG CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    黄勇; 崔社怀

    2011-01-01

    [Objective]To identify the influences of two delivery ways, bronchial arterial infusion and intravenously guttae, of paclitaxel liposome on the chemotherapy for advanced non small cell lung carcinoma.[Methods]Total 32 patients with advanced non small cell lung carcinoma were treated with paclitaxel liposome and nedaplatin through bronchial arterial infusion or peripheral vein instillation respectively.The ratios of treatment response and adverse reaction were compared.[Results]Compared with intravenously guttae groups, the overall remission rate on solid tumor increased obviously and incidence rate of bone marrow depression, neurotoxicity, arthralgia and myalgia decreased significantly.So the patients were more easily to tolerate.[Conclusion]For the patients with advanced non small cell lung carcinoma, the chemotherapy with paclitaxel liposome through bronchial arterial infusion would decrease drug toxic reactions and elevate clinic curative effects obviously.%[目的]明确支气管动脉灌注和常规静脉滴注两种不同给药方式对晚期非小细胞肺癌紫杉醇脂质体化疗的影响.[方法]紫析醇脂质体联合奈达铂,分别通过外周静脉滴注和支气管动脉灌注两种方式应用于共32例晚期非小细胞肺癌患者,比较治疗有效率及不良反应发生率.[结果]与静脉给药组相比,支气管动脉灌注组实体瘤总有效率明显增高,且骨髓抑制、神经毒性及关节肌肉痛等药物毒性反应明显减少,患者更易耐受.[结论]紫析醇脂质体通过支气管动脉灌注方式应用于晚期非小细胞肺癌患者的化疗,不仅可以明显减少药物的毒性反应,还能够提高临床疗效.

  2. Observation on Clinical Efficacy of Self-Made Lung Cancer Prescription Combined with Pemetrexed and Cisplatin in the Treatment of Intermediate and Advanced Stage Non-Small Cell Lung Cancer%自拟肺癌方联合培美曲塞及顺铂治疗中晚期非小细胞肺癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    于小伟; 徐川; 方美花; 仝欣; 李敏

    2015-01-01

    Objective :To observe the clinical efficacy of pemetrexed and cisplatin in combination with self-made lung cancer prescription in the treatment of intermediate and advanced stage non-small cell lung cancer .Methods : A total of 71 patients with intermediate or advanced stage non-small cell lung cancer diagnosed by imaging and pathological or cytological method from Oct .2010 to Oct .2013 were randomly divided into 2 groups .The 35 cases in control group received chemotherapy using pemetrexed combined with cisplatin ,and the 36 cases in treatment group received self-made lung cancer prescription orally in combination with the same chemotherapy of control group . Results : The total effective rates of improvement on clinical symptoms ,quality of life and immune index in the treatment group were superior to those in the control group(P 0 .05) .Conclusions : Integrated Chinese and Western medicine show certain efficacy in the treatment of intermediate and advanced stage non-small cell lung cancer ,and thus is worthy of clinical promotion .%目的:观察培美曲塞联合顺铂方案(PC 方案)化疗加自拟肺癌方口服治疗中晚期非小细胞肺癌的临床疗效。方法:将2010年10月—2013年10月经影像学及病理或细胞学确诊为中晚期非小细胞肺癌的患者71例随机分为两组,治疗组36例,对照组35例。对照组给予 PC 方案化疗,治疗组在对照组的基础上给予自拟肺癌方口服。结果:治疗组在临床症状改善、生存质量提高、免疫指标变化方面的总有效率均优于对照组(P<0.05),但肿瘤客观疗效有效率及临床受益率、体质量变化总有效率与对照组比较差异无统计学意义(P>0.05)。结论:中西医结合治疗中晚期非小细胞肺癌疗效肯定,有临床推广价值。

  3. Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study.

    Science.gov (United States)

    Sánchez-Lara, Karla; Turcott, Jenny G; Juárez, Eva; Guevara, Patricia; Núñez-Valencia, Carolina; Oñate-Ocaña, Luis F; Flores, Diana; Arrieta, Oscar

    2012-01-01

    Early identification and treatment of nutritional deficiencies can lead to improved outcomes in the quality of life (QoL) and survival of patients with nonsmall cell lung cancer (NSCLC). Noninvasive techniques are needed to evaluate changes in body composition as part of determining nutritional status. The aim of the study was to evaluate the association of nutritional parameters in health-related quality of life (HRQL) and survival in patients with advanced NSCLC. Chemotherapy-naïve patients with advanced NSCLC with good performance status Eastern Cooperative Oncology Group (ECOG) 0-2 were included prospectively in the study. We evaluated inflammatory parameters such as C-reactive protein, platelet/lymphocyte index, neutrophil/lymphocyte index, serum interleukin (IL)-6, and tumor necrosis factor-α, and nutritional variables such as body mass index (BMI) and serum albumin levels. Bioelectrical impedance analysis including phase angle was obtained before cisplatin-based chemotherapy was started. HRQL was assessed by application of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13 instruments at baseline. Overall survival (OS) was calculated with the Kaplan-Meier method and analyzed with log-rank and Cox proportional hazard models. One hundred nineteen patients were included. Mean BMI was 24.8 ± 4.5 kg/m(2), average weight loss of patients was 8.4%, and median phase angle was 5.8°. Malnutrition measured by subjective global assessment (SGA), weight loss >10%, BMI >20 was associated with lower HRQL scales. Patients with ECOG 2, high content serum IL-6, lower phase angle, and malnutrition parameters showed lower OS; however, after multivariate analysis, only ECOG 2 [Hazard ratio (HR), 2.7; 95% confidence interval (95% CI), 1.5-4.7; P = 0.001], phase angle ≤5.8° (HR = 3.02; 95% CI: 1.2-7.11; P = 0.011), and SGA (HR = 2.7; 95% CI, 1.31-5.5; P = 0.005) were associated with poor survival. Patients

  4. Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Ravi B. [Harvard Medical School, Boston, Massachusetts (United States); Cronin, Angel M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Kozono, David E.; Oxnard, Geoffrey R.; Mak, Raymond H.; Jackman, David M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Lo, Peter C. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Baldini, Elizabeth H.; Johnson, Bruce E. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Chen, Aileen B., E-mail: achen@lroc.harvard.edu [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2014-07-15

    Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

  5. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  6. Isolating the Role of Bevacizumab in Elderly Patients With Previously Untreated Nonsquamous Non–Small Cell Lung Cancer

    Science.gov (United States)

    Socinski, Mark A.; Patel, Jyoti D.; Sandler, Alan B.; Schiller, Joan H.; Leon, Larry; Hazard, Sebastien J.; Ramalingam, Suresh S.

    2016-01-01

    Background: Patient-level data from 2 phase III studies in patients with previously untreated, advanced-stage, nonsquamous non–small cell lung cancer (NSCLC) were pooled to examine outcomes with bevacizumab and chemotherapy based on age. Methods: Data from patients randomized to paclitaxel–carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 (E4599) and PointBreak studies were pooled and compared with E4599 patients randomized to PC alone. Patients were grouped by age: below 65, 65 to 74, 70 to 74, below 75, and 75 years or above. A multivariable model was used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using time-to-event outcomes. Adverse events (AEs) were assessed by age group in each study. Results: The PC+bevacizumab and PC arms comprised 901 and 444 patients, respectively. PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.89), 65 to 74 years (HR, 0.80; 95% CI, 0.64-1.00), 70 to 74 years (HR, 0.68; 95% CI, 0.48-0.96), and below 75 years (HR, 0.78; 95% CI, 0.68-0.89) but not in those aged 75 years or above (HR, 1.05; 95% CI, 0.70-1.57). Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years (63% vs. 48%; P<0.05) and 75 years or above (81% vs. 56%; P <0.05) in E4599. Conclusions: This analysis suggests that the survival benefits associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC; no benefit, however, was observed for bevacizumab-eligible patients who were 75 years or above. PMID:25628268

  7. 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

  8. Drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors in treatment of advanced non-small cell lung cancer——A new dawn in challenge%晚期非小细胞肺癌EGFR-TKIs治疗的耐药机制研究——挑战中蕴含新的曙光

    Institute of Scientific and Technical Information of China (English)

    吴国明; 钱桂生

    2012-01-01

    Currently, molecularly target therapy has increasingly altered the strategies in advanced non-small cell lung cancer ( NSCLC). Epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs) , gefitinib and erlotinib, are regarded as the most successful target drugs. However, EGFR-TKIs resistance has become a major clinical challenge. EGFR-TKIs resistance includes the primary resistance and the acquired resistance. The primary resistance' s mechanisms are associated with other non-sensitive EGFR mutations such as exon 20 insertions and other gene mutations such as KRAS, BRAF and EML4-ALK. The acquired resistance' s mechanisms are often associated with the secondary T790 mutation and MET gene amplification. At present, new strategies in overcoming EGFR-TKIs resistance are mainly focusing on irreversible EGFR inhibitors and MET inhibitors.

  9. 现行晚期非小细胞肺癌治疗策略%A systematic review of the treatment strategies for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    程颖; 李鑫; 刘文超

    2011-01-01

    肿瘤分子标志物的应用对肺癌化疗药物的选择及预测治疗效果有重要意义.对于具有良好行为状态(performance status,PS)评分的患者,以铂类为基础的双药联合治疗方案可延长生存期、改善生活质量、减少肿瘤相关症状.对于PS评分差的或高龄患者推荐单药化疗.二线治疗的选择包括:多西他赛、培美曲塞、吉非替尼和厄洛替尼.其中,培美曲塞对于非鳞癌患者可获益,吉非替尼则应用于EGFR突变患者.尽管治疗方法和可选择的药物不断发展,晚期非小细胞肺癌患者生存期仍有限,新的治疗方法和临床研究都有待进一步探索.%Lung cancer is the world's leading reasons of cancer caused death. The majority of patients bear nonsmall cell lung cancer ( NSCLC ). And most of them have already locally advanced or distant metastasis when clinical diagnose. The most common histological type is adenocarcinoma, followed by squamous cell carcinoma, large cell carcinoma and undifferentiated carcinoma, et al. For patients of good performance status ( PS ) scores, platinum -based double - agent regimen could prolong survival period, improve quality of life and reduce tumor - related symptoms. Without clinical benefit, the addition of a third cytotoxic drug could only increase toxicity. It's tumor molecular markers that show great significance on chemotherapy drug options and treatment efficacy prediction. Patients will receive better survival benefits if we combines platinum -based double -agent regimen with molecular targeted drug,such as bevacizumab. Such patients must meet non -squamous cell carcinoma, PS score ≤ 1, no brain metastases,no hemoptysis, no uncontrolled hypertension and no need of anticoagulant therapy. Low PS score patients, as chemotherapy brings little clinical benefits, are currently recommended single -agent chemotherapy. It's also the standard chemotherapy of most elderly patients ( ≥ 70 years old ), who are thought to

  10. BRAF mutation and BRAF-targeted therapy:recent advances in non-small cell lung cancer%非小细胞肺癌BRAF突变及靶向治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    张静(综述); 樊旼(审校)

    2015-01-01

    BRAF mutation is one of driver mutations in non⁃small cell lung cancer(NSCLC). BRAF mutation rate is about 0�5%~4�9%, and more than half of BRAF mutation is V600E. BRAF mutation occurs more commonly in female patients with adeno⁃carcinoma, and the mutation rate is much lower in Asian people. The clinical significance of coexistence of BRAF mutation and other mutations, such as EGFR and K⁃Ras mutations was yet unknown. Given the huge global burden of lung cancer, progress of BRAF mu⁃tation studies hold significant importance, despite its low mutation rate overall. Currently, several BRAF inhibitors are being studied in clinical trials for patients with NSCLC. This review is intended to outline the recent advances of BRAF mutation and its targeted therapy in NSCLC.%鼠类肉瘤病毒癌基因同源物B1( BRAF)基因是非小细胞肺癌( NSCLC)的驱动基因之一,在NSCLC中突变率为0�5%~4�9%,其中V600E突变类型占到一半以上。 BRAF突变多见于女性、肺腺癌患者,亚裔人群中突变率相对较低。BRAF突变可与其他基因突变,如EGFR、K⁃Ras突变共存,但其临床意义尚不清楚。全球NSCLC患者数量庞大,尽管BRAF突变率在NSCLC中较低,低突变率基因及其靶向治疗的研究仍然相当重要。目前BRAF抑制剂治疗NSCLC正在临床试验中。本文就NSCLC中BRAF突变及靶向治疗的研究进展进行综述。

  11. Targeted therapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Ching Tang

    2004-01-01

    @@ 1 Introduction Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

  12. Circulating Nucleosomes Predict the Response to Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer Reviewed Concurrently with Investigational Strategy for Personalized Therapy of Chemotherapy for Lung Cancer%监测血循环中核小体来预测晚期非小细胞肺癌的化疗敏感性--兼评肺癌个体化治疗的研究策略

    Institute of Scientific and Technical Information of China (English)

    顾春东; 王震

    2006-01-01

    @@ 1文献类型 治疗. 2证据水平 3a.2004年影响因子:5.623. 3文献来源 Holdenrieder S, Stieber P, von Pawel J, et al.Circulating nucleosomes predict the response to chemotherapy in patients with advanced non-small cell lung cancer [J]. Clin Cancer Res, 2004, 10(18Pt 1) :5981-5987.

  13. Clinical observation of docetaxel plus cisplatin versus gemcitabine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer%多西他赛与吉西他滨分别顺泊治疗晚期非小细胞肺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    Yongguang Cai; Ming Li; Xin Xie

    2011-01-01

    Objective: The aim of this study was to evaluate the clinical efficacy and side effects of docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment in the patients with advanced non-small-cell lung cancer (NSCLC). Methods: Seventy-six patients with advanced NSCLC who were chemotherapy-naive were enrolled in two groups. In docetaxel group (DP group) the patients received docetaxe175 mg/m2 and cisplatin 60 mg/m2 on day 1. In gemcitabine group (GP group) the patients received gemcitabine 1000 mg/m2 on day 1 and day 8. The dosage of cisplatin was the same as DP group. The two regiments were administrated intravenously every 21 days as a cycle, each patient received 2-4 cycles. All patients were followed up until disease progressed or patients died. Results: The overall response rates were 43.5% in DP group and 45.9% in GP group. The response rate was significantly different between the initial treated group and retreated group in both two groups (53.8% vs 23.0% in DP group and 56% vs 25% in GP group, P < 0.05, respectively). The main side effects were bone marrow suppression and thrombocytopenia. Conclusion: Docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment for the patients with advanced NSCLC were efficient and well-tolerated chemotherapeutic approachs with Iow toxicity levels. The efficacy and major toxicity in two groups were similar.

  14. 康艾注射液辅助化疗对晚期非小细胞肺癌患者血清VEGF表达的干预作用%Intervention Effects of Adjuvant Chemotherapy Combined with Kang'ai Injection on Expression of Serum VEGF in Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    张梅春; 赵子文; 曾军; 刘朝晖

    2011-01-01

    Objective To explore the effects of adjuvant chemotherapy combined with Kang'ai injection on the expression of serum VEGF in patients with advanced non-small cell lung cancer. Methods Forty-six patients with advanced non-small cell lung cancer were randomly divided equally into two groups. Patients in experimental group were treated with gemcitabine and cisplatin chemotherapy regimen(GP)combined with Kang'ai injection, while patients in the control were just treated with GP regimen chemotherapy. The expression levels of serum vascular endothelial growth factor(sVEGF) were measured by ELISA before and after the treatment,respectively. Results The sVEGF levels of all patients with advanced NSCLC were obviously higher than that of health controls(P<0. 05). And the level of sVEGF in squamous cell cancer group was higher than that in adenocarcinoma, large cell carcinoma or adenosquamous carcinoma group, respectively(P<0. 05),while there was no significant difference between the latter 3 groups(P>0. 05). Compared the well differentiated group, the sVEGF level of moderately and poorly defferentiated group was increased with no significance(P>0. 05). The sVEGF level was obviously decreased in two groups after the treatments(P<0. 05). Furthermore, the sVEGF level was significantly decreased combination therapy group than that in chemotherapy group(P<0. 05). Conclusion Kang'ai injection might decrease the expression of serum VEGF in patients with advanced non-small cell lung cancer which suppressed neovascularization. Serum VEGF could be a biomarker for lung cancer diagnosis and therapeutic effect of chemotherapy or biotherapy.%目的 探讨康艾注射液辅助化疗对晚期非小细胞肺癌患者血清VEGF(sVEGF)表达的干预作用.方法 将入组的46例晚期非小细胞肺癌患者随机分为实验组(康艾注射液联合化疗组,23例)和对照组(单纯化疗组23例),应用酶联免疫吸附法(ELISA)检测患者治疗前后sVEGF表

  15. Progress of molecular-targeted therapy of EGFR-TKIs for advanced non-small cell lung cancer%晚期非小细胞肺癌表皮生长因子受体-酪酸激酶抑制剂靶向治疗进展

    Institute of Scientific and Technical Information of China (English)

    洪群英; 白春学

    2012-01-01

    With the progress of molecular biology, targeted therapy especially epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) become an important approach in the treatment of lung cancer. EGFR-TKIs are effective in either first, second and third-line treatment and maintenance therapy for advanced non-small cell lung cancer (NSCLC). This review describes progress of molecular-targeted therapy of EGFR-TKIs for advanced NSCLC.%随着分子生物学研究的深入,靶向治疗特别是表皮生长因子-酪氨酸激酶抑制剂(EGFR-TKI)为肺癌治疗开辟了蹊径.EGFR-TKI无论作为一线还是二、三线治疗或维持治疗对晚期非小细胞肺癌(NSCLC)均有效.本文概述EGFR-TKI在晚期NSCLC治疗中的应用进展.

  16. 吉西他滨与三维适形放疗同步治疗局部晚期非小细胞肺癌的临床观察%Clinical observation of gemcitabine and concomitant three-dimensional conformal radiotherapy in the treatment of locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jing Cheng; Gang Wu; Hongge Wu; Jun Xue

    2008-01-01

    Objective:To evaluate lhe clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy(3D-CRT)for locally advanced non-small cell lung cancer(NSCLC).Methods:From April 2002 to June 2005,38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously.Chemotherapy consisted of intravenously gemcitabine 350 mg/m2 on days 1,8,15,22,29,36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day,5 days per week.Results:The overall response rates of primary tumor and mediastinum metastatic node were 86.8%(33/38)and 90.6%(29/32)respectively,and 91.7%(22/24)and 78.6%(11/14)for squamous cell carcinoma and adenocarcinoma respectively.The acute side effects of patients were mostly myelosuppression,nausea,vomiting,radiation-induced esophagitis and pneumonitis(RTOG Ⅰ/Ⅱ),however,all of them were cured.Conclusion:Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.

  17. Clinical study of docetaxel-vinorelbine as second-line chemotherapy in advanced non-small cell lung cancer%多西紫杉醇联合长春瑞滨二线治疗晚期非小细胞肺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    Jun Guo; Weiping Li; Degang Song; Zhehai Wang; Jie Liu; Changzheng Li; Zhen Chen; Huan Shi

    2008-01-01

    Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.

  18. 参麦注射液防治晚期非小细胞肺癌化疗不良反应的临床观察%Clinical observation of Shenmai injection in the treatment for adverse reactions of chemotherapy on advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To observe the efficacy of Shenmai injection in the treatment for adverse reactions of chemotherapy on advanced non-small cell lung cancer(NSCLC).Methods: 45 NSCLC patients with stages Ⅲb-IV were randomly divided into two groups: the treatment group(treated by chemotherapy combined with Shenmai injection)and the control group (treated by chemotherapy only).The efficacy of the two groups was evaluated after 3 cycles of treatment.Results: There was no significant difference between the two groups in the recent curative effects(P>0.05), while there were significant differences between them in Karnofsky score and weight(P<0.05).The treatment group was better than the control group in preventing leucopenia and decreased hemoglobin, and significant differences were found between them(P<0.05).The incidence of thrombocytopenia, nausea and vomiting, hepatic and renal dysfunction in the treatment group was lower than that in the control group, but no significant differences were found between them(P>0.05).Conclusion: Shenmai injection would not influence the efficacy of chemotherapy on advanced NSCLC patients, while it could improve the quality of life, increase the body weight of patients, alleviate adverse reactions of chemotherapy as myelosuppression so as to improve the tolerance of organism to chemotherapy.

  19. 局部晚期非小细胞肺癌患者同步放化疗医院感染的病原学分析及预防%Etiology of nosocomial infections in locally advanced non-small cell lung cancer patients undergoing chemoradiotherapy and the prevention

    Institute of Scientific and Technical Information of China (English)

    林白桦; 贾勇士; 毕爱红; 吴树强

    2012-01-01

    目的 探讨局部晚期非小细胞肺癌患者同步放(化)疗医院感染的病原学情况及预防对策.方法 选取2007年1月-2010年1月84例进行同步放(化)疗的局部晚期非小细胞肺癌并发医院感染的患者为研究对象,将其医院感染的发生率、病原菌分布、危险因素及临床对策进行研究.结果 84例患者中以肺部感染所占比例最高,达46.43%,其次为口咽部、胃肠道及泌尿道,分别占19.05%、15.48%及13.09%;而病原菌以革兰阴性菌为主,占47.67%,其次依次为革兰阳性菌占37.21%、真菌占15.12%;患者年龄、营养状况、合并其他基础疾病种类、有侵入性操作、住院时间≥14d、应用抗菌药物≥3种为医院感染的危险因素(P<0.05);所有患者经针对性的治疗后感染得到有效控制.结论 局部晚期非小细胞肺癌同步放(化)疗医院感染患者的感染部位及病原菌分布均有其特殊性,给予针对性的治疗可改善预后.%OBJECTIVE To investigate the etiology of nosocomial infections in locally advanced non-small cell lung cancer patients who underwent chemoradiotherapy and propose prevention countermeasures. METHODS A total of 84 patients with nosocomial infections who underwent synchronous chemoradiotherapy for locally advanced non-small cell lung cancer from Jan 2007 to Jan 2010 were chosen as the research objects. The incidence of nosocomial infections, distribution of the pathogens , risk factors and clinical strategies were studied. RESULTS In the 84 patients, the rate of lung infections was the highest (46. 43%) , followed by the oropharynx infections (19. 05%) , gastrointestinal tract infections (15. 48%) and urinary tract infections (13. 09%); and gram-negative bacteria were dominated in the pathogens, accounting for 47. 67%, followed by gram-positive bacteria (37. 21%) and fungi (15. 12%); the age , nutrition status, combination with other underlying diseases, invasive operation, hospital

  20. 芪参扶正胶囊联合TP方案对晚期非小细胞肺癌脾肾亏虚型患者生活质量的影响%The influence of Qishenfuzheng capsule combined with TP in improving the quality of life of patients with advanced non-small cell lung cancer of spleen and kidney deficiency type

    Institute of Scientific and Technical Information of China (English)

    张子志; 张永杰

    2016-01-01

    Objective To evaluate the efficacy and safety of Qishenfuzheng capsule combined with TP in improving the quality of life of patients with advanced non-small cell lung cancer of spleen and kidney deficiency type. Methods37 cases of patients with advanced non-small cell lung cancer proposed TP chemotherapy in Department of Internal Medicine-Oncology of Shouguang Traditional Chinese Medicine Hospital from March 2012 to February 2015 were selected and divided into therapy group (18 cases) and control group (19 cases) with the ratio of 1: 1 parity packets. Patients in therapy group were treated with Qishenfuzheng capsule combined with TP chemotherapy. Patients in control group were treated with TP chemotherapy.ResultsCompared with before treatment, field of role function, physical function and emotional function of therapy group were significantly improved, the differences were significant (P<0.05).TCM clinical symptom score of therapy group was significantly reduced,the difference was significant (P<0.05).KPS score after treatment was significantly higher than that of control group, the difference was statistically significant (P<0.05).Hematologic toxicity and gastrointestinal reactions of therapy group were much better than those of control group.ConclusionQishenfuzheng capsule could improve the quality of life of patients with advanced non-small cell lung cancer (NSCLC) of spleen and kidney deficiency type, and could reduce the toxicity of chemotherapy drugs.%目的:评价芪参扶正胶囊联合TP方案在提高脾肾亏虚型晚期非小细胞肺癌生活质量方面的有效性、安全性。方法选择寿光市中医医院肿瘤科2012年3月~2015年2月拟TP方案化疗的晚期非小细胞肺癌37例,按1∶1的比例奇偶分组,治疗组18例,对照组19例治疗组采用芪参扶正胶囊加TP化疗方案。对照组采用TP方案化疗。结果治疗组的角色功能、躯体功能、情绪功能领域有明显改善,与治疗前比较,

  1. 62例不可手术的局部晚期非小细胞肺癌同步放化疗分析%Clinical analysis of concurrent chemoradiotherapy of 62 patients with inoperable locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    孙志华; 李青峰; 伍钢

    2012-01-01

    目的:评价局部晚期不可手术的非小细胞肺癌同步放化疗的疗效和安全性.方法:对62例经细胞学或病理学明确诊断的局部晚期非小细胞肺癌患者进行同步放化疗,4个周期的NP加上同步放疗,第1周期NP化疗第1天就开始实施放疗.放疗采用15MV -X线,3D - CRT常规分割照射,总剂量60Gy.结果:可评价的60例患者,完全缓解11例,部分缓解36例,稳定11例,进展2例,总有效率为78.3%,1年、2年、3年生存率分别为90%,48.3%和23.3%,中位生存时间为23.2个月.结论:疗前正确评估合适的局部晚期非小细胞肺癌患者,同步放化疗有较好的1年、2年、3年生存率及中位生存时间,毒副反应多能耐受.%Objective:To evaluate the efficacy and safety of concurrent chemoradiotherapy in patients with locally advanced non - small cell lung cancer. Methods: All 62 patients diagnosised as locally advanced non - small cell lung cancer by clear cytology or pathology accepted 3D - CRT of thoracic radiotherapy and concurrent chemotherapy of NP. 3D - CRT, started on day I in the first cycle of NP chemotherapy. Chemotherapy was carried out for 4 cycles, every cycle 21 days. Thoracic radiotherapy adopted 3D - CRT of 15MV - X ray with conventional fractionated irradiation, a total dose of 60 Gy. Results; In 60 evaluable patients, there were 11 cases complete response 36 cases had partial response (PR) , llcases with no change(NC) and 2 cases with progression disease (PD). The overall response rates were 78.3% .1,2,3 year survival rate was 90% ,48.3% and 23.3% , respectively, and a median survival time was 23.2 months. Conclusion: For patients with locally advanced unresectable non -small cell lung cancer concurrent chemoradiotherapy is effective and have a good 1,2,3- year survival rate, median survival time, and side effects are tolerable.

  2. Traditional Chinese Medicine in Combination with Chemotherapy for Senile Mid-advanced Non-small Cell Lung Cancer: A Systematic Review%中化联合治疗老年中晚期非小细胞肺癌系统评价

    Institute of Scientific and Technical Information of China (English)

    荣震; 韦海霞; 黄瀚斐

    2012-01-01

    Objective: To compare and assess the. effectiveness and safety of Traditional Chinese Medicine in combination with chemotherapy versus chemotherapy for senile mid-advanced non-small cell lung cancer. Methods : To collect all of RCTs with Traditional Chinese Medicine in combination with chemotherapy versus chemotherapy for senile mid-advanced non-small cell lung cancer from the Cochrane library, Medline, Embase, Springer link, CNKI, VIP and Wanfang in the internet. The published time of all studies was from Jan. 1996 to Nov.2011. The language included English and Chinese. Finally the data of chosen studies was analyzed according to the Cochrane Handbook for Systematic Reviews. Result: Eighteen studies involving 1108 patients were included, with 578 patients in the experimental group of Traditional Chinese Medicine in combination with chemotherapy and the rest in the control group of chemotherapy. The experimental group was superior to the control group in prolonging overall survival, enhancing the quality of life and clinical effectiveness, being lower adverseness in thrombopenia, anemia, digestive reaction and hepatic injury. But the two groups had no significance of difference in leuoopenia and renal injury. Conclusion : The regimen of traditional Chinese medicine in combination with chemotherapy is more appropriate for the treatment of, senile mid-advanced non-small cell lung cancer.%目的:评价中化联合治疗老年中晚期非小细胞肺癌(NSCLC)的临床获益及安全性.方法:计算机检索Cochrane library、Medline、Embase、Springer link、NCKI、VIP、万方数据库,检索时限:1996-01/2011-11.检索文种不限制.收集所有中药联合化疗治疗老年中晚期NSCLC的随机对照试验(RCT),筛选出符合纳入标准的文献,经质量评价后,采用Cochrane协作网提供的RevMan5.1.0软件对纳入研究结果进行Meta分析.结果:共检索到相关文献140篇,最终纳入18个RCT.Meta分析结果显示:中化联合方案在生

  3. 局部晚期非小细胞肺癌3DCRT 联合同步化疗的临床疗效观察%Observation of clinical effect by 3DCRT combined with concurrent chemotherapy for locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    张德智; 王岩; 王璐瑶

    2016-01-01

    Objective To observe and analyze clinical effect by three dimensional conformal radiation therapy (3DCRT) combined with concurrent chemotherapy in the treatment of locally advanced non-small cell lung cancer. Methods A total of 68 patients with locally advanced non-small cell lung cancer were divided by different treatment measures into concurrent chemotherapy group and sequential chemotherapy group, with 34 cases in each group. Concurrent chemotherapy group received 3DCRT combined with concurrent chemotherapy, while sequential chemotherapy group received chemotherapy after 3DCRT. Curative effects were compared between the two groups. Results There was no statistically significant difference of effective rate between concurrent chemotherapy group as 70.59% and sequential chemotherapy group as 64.71% (P>0.05). Concurrent chemotherapy group had 2-year survival rate as 38.2% (13/34), and that in sequential chemotherapy group was 26.5% (9/34). Median survival time was 17.0 months in concurrent chemotherapy group and 13.0 months in sequential chemotherapy group. Test by log-rank showed better survival rate in concurrent chemotherapy group than sequential chemotherapy group (χ2=4.83, P0.05)。同步化疗组2年生存率为38.2%(13/34),序贯化疗组为26.5%(9/34);同步化疗组中位生存期为17.0个月,序贯化疗组为13.0个月,采用 log-rank 检验,结果显示同步化疗组生存率优于序贯化疗组(χ2=4.83, P<0.05)。结论3DCRT 联合同步化疗治疗局部晚期非小细胞肺癌效果优于序贯化疗,两种治疗方法不良反应无差异,患者均可耐受。

  4. EGFR-TKIs 联合放疗在局部晚期非小细胞肺癌治疗中的地位和作用%The situation and application of EGFR-TKIs combined with radiotherapy in treating local advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    赵俊华; 范增慧; 赵玉霞

    2012-01-01

    The standard treatment for those unresectable regional advanced non - small cell lung cancer(NSCLC) is concurrent chemo -radiotherapy. For those NSCLC patients with epidermal growth factor receptor (EGFR) exons 19, 21 positive mutation, the administration of EGFR tyrosine kinase inhibitor (EGFR -TKIs) shows great benefit in survival. Radiotherapy has specific regional advantage comparing with surgeiy and chemotherapy. Radiotherapy might activate EGFR signal pathway, induce cell proliferation and enhance DNA repair, so as to leading to the resistance of radiotherapy. So EGFR -TKIs might have the effect of radiotherapy sensibilization. In clinic,the combination of EGFR - TKIs and radiotherapy for regional advanced or metastasis NSCLC shows tolerable side - effect and different survival which might be the effect of different patients chosen. More large samples and multi - centers clinical research of concurrent personal EFGR — TKIs and radiotherapy for unresectable NSCLC with EFGR gene mutation is needed, which may be a kind of first — line treatment in future.%不可手术切除的局部晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)从组织分型看,标准治疗模式为同期化放疗,但从分子分型看,表皮生长因子受体(epidermal growth factor receptor,EGFR)外显子19、21突变阳性的NSCLC患者一线应用EGFR酪氨酸激酶抑制剂(EGFR-TKIs),将在生存上最大程度地获益.放疗具有手术不可比拟的空间和化疗无法取得的局部优势,放疗可激活EGFR信号通路,通过诱导细胞增殖和增强DNA修复而导致放疗抵抗,EGFR-TKIs具有放疗增敏作用.临床研究结果提示EGFR-TKIs联合胸部放疗治疗局部晚期或转移NSCLC患者,总体上毒性反应可以耐受,但生存获益程度不一,可能与病例选择不同有关.对于EGFR基因突变的不可切除的NSCLC患者,EGFR-TKIs同步个体化放疗目前缺乏大样本多中心的临床研究结果,也许是今后一线治疗的一种选择.

  5. Changes of Th17 and Treg Cells in the Peripheral Blood of Patients with Advanced Non-small Cell Lung Cancer Before and After Chemotherapy%中晚期非小细胞肺癌患者外周血Treg、Th17细胞化疗前后的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    赵丽丽; 张良明

    2015-01-01

    目的:分析中晚期非小细胞肺癌患者化疗前后外周血中 Treg 细胞和 Th17细胞比例变化及临床意义。方法收集51例中晚期非小细胞肺癌患者(观察组)化疗前后及47例健康对照组外周血标本,应用流式细胞术检测 Treg 细胞和 Th17细胞所占 CD4+ T 细胞的比例,观察 Treg 和 Th17细胞比例在化疗前后的变化及其相关性。结果化疗后缓解组外周血中 Th17及 Treg 细胞比例较化疗前降低(P 0.05)。非缓解组2种细胞的比例较化疗前增高(P 0. 05), but the proportion of Treg cells of the remission group was higher significantly(P < 0. 05). The proportion of Th17 and Treg cells of the non-remission group after chemotherapy were all significantly higher than before chemotherapy (P < 0. 05),and were higher than those of the control group(P < 0. 05). The proportion of Th17 cells were posi-tively related to the proportion of Treg cells in the peripheral blood of patients with advanced non-small cell lung cancer before and after chemotherapy(r = 0. 589,0. 657;P < 0. 05). Conclusion Chemotherapy can reduce the proportion of Th17 cells and Treg cells in the peripheral blood of patients with advanced non-small cell lung cancer, and has the positive significance for tumor immune function.

  6. Therapeutic vaccines in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Socola F

    2013-09-01

    Full Text Available Francisco Socola,1 Naomi Scherfenberg,2 Luis E Raez3 1Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 2University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 3Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, Florida, USA Abstract: Non-small cell lung cancer (NSCLC unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-β in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3, an antigen-based vaccine, has shown promising results in MAGE-A3+ NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin 1 protein (MUC-1, a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF vaccine that induces anti-EGF antibody production and prevents EGF

  7. Therapeutic effect between Pemetrexed disodium and Docetaxel as second line chemotherapy on advance non-small cell lung cancer%培美曲塞与多西他赛二线随机分组治疗晚期非小细胞肺癌对比分析

    Institute of Scientific and Technical Information of China (English)

    郑积华; 林金容; 谢波; 周娟; 徐志勇; 黄雪琴; 王仙赐; 张为民

    2013-01-01

    OBJECTIVE: To compare therapeutic effects between pemetrexed disodium and docetaxel as second line chemotherapy on advanced non-small cell lung cancer. METHODS: Eighty patients with advance non-small cell lung cancer resistant to first line chemotherapy were enrolled. Fifty-one cases had finished first line chemotherapy with paclitaxel and cis-platin or carboplatin (TP or TO. Twenty-one cases had finished first line chemotherapy with gemzar and cis-platin or carboplatin (GP or GO ,8 cases had carried out first line chemotherapy with nolvebin and cis-platin or carboplatin (NP or NC. A dose of 500 mg/m2 pemetrexed disodium or 75 mg/m2 docetaxel was respectively administered intravenously once every 21 days. RESULTS: The therapeutic effect rates in pemetrexed disodium group and docetaxel group were 7. 3% (3/41) and 5. 1 % (2/39) respectively (P>0. 05). Disease control rates in pemetrexed disodium group and docetaxel group were 46. 3%(19/41) and 33. 3% (13/39) respectively (P>0. 05). Overall survival in pemetrexed disodium group was 3. 1 — 15. 6 months (medium time 7. 6 months) while overall survival in docetaxel group was 4. 4 — 12. 6 months(medium time 8. 1 months). Time to progression in pemetrexed disodium group was 4. 9 months while time to progression in docetaxel group was 3. 9 months. Survival rates of one year were 26. 8%(11/41) in in pemetrexed disodium group and 2. 6% (1/39) in docetaxel group respectively. The main adverse effects in both group were slight and acceptable,which included neutropenia, rash, arthragia, alopecia, diarrhea, anorexia, nausea, vomiting, dizziness, headache, chest distress and abdominal pain. No patients showed abnormality in liver or kidney function. No patients showed abnormality in electrocardiogram. CONCLUSION; Single pemetrexed disodium or do cetaxel as second line chemotherapy in the treatment of patients with advanced refractory non-small cell lung cancer was safe and effect and both of them can be a choice of second line

  8. Photodynamic therapy for the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Friedberg, Joseph S; Glatstein, Eli; Stevenson, James P; Sterman, Daniel H; Hahn, Stephen M; Cengel, Keith A

    2012-02-01

    Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described.

  9. Advance in MicroRNAs and EGFR-TKIs Secondary Resistance Research in Non-small Cell Lung Cancer%非小细胞肺癌中microRNAs与EGFR-TKIs继发性耐药机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    段晓阳; 史健

    2014-01-01

    近年来,在非小细胞肺癌(non-small cell lung cancer, NSCLC)靶向治疗中,尤其是伴有表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变的患者,EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor, TKI)越来越多地进入到临床治疗,但EGFR-TKI耐药的产生不仅影响药物敏感性,甚至出现疾病进展,成为制约其疗效的主要瓶颈。微小RNA(microRNAs, miRNAs)是一种非编码蛋白的RNA,参与转录后水平基因的表达调控,最近研究发现,miRNAs参与了EGFR-TKIs耐药,影响肿瘤细胞对吉非替尼的敏感性。本文就NSCLC中miRNAs与EGFR-TKIs继发性耐药之间的相关性研究进展做简要的综述。%In recent years, in non-small cell lung cancer (NSCLC) targeted therapy, especially in patients with epidermal growth factor receptor (EGFR) mutations, EGFR-tyrosine kinase inhibitors (TKI) more and more come into the clinical treatment, but EGFR-TKI resistance not only inlfuence the drug sensitivity, appear even disease progression, become the main bottleneck of its curative effect. MicroRNAs (miRNAs) is a non coding RNA and protein involved in regulating gene expression in the transcription level. Recent studies found that miRNAs involved in EGFR-TKIs resistance, which affect the sensitivity of tumor cells to treatment. In this paper, we reviewed brielfy advance in miRNAs and EGFR-TKIs secondary resis-tance research in NSCLC.

  10. Progress in patients with EGFR sensitive mutation advanced non-small cell lung cancer:comparison of therapeutic efficacy of EGFR-TKI as first- or second-line therapy%EGFR-TKI治疗EGFR敏感突变的晚期NSCLC一线与二线疗效对比的研究进展

    Institute of Scientific and Technical Information of China (English)

    应梦洁(综述); 孙建立(审校)

    2016-01-01

    本文对近年来关于表皮生长因子络氨酸激酶抑制剂(EGFR-TKI)的多项研究进行分析:EGFR-TKI与传统化疗相比,无论一线还是二线治疗表皮生长因子(EGFR)突变的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者均能够提高客观缓解率(objective response rate,ORR),延长无进展生存期(progression free survival,PFS),改善生活质量;应尽早明确患者基因突变状态,二线治疗进行基因检测也是十分必要的;对于EGFR敏感突变的患者,有研究显示EGFR-TKI一线治疗与二线治疗相比,能提高有效率及疾病控制率,但并未见PFS及总生存期(overall survival,OS)的延长。%hTe article discusses a number of studies on epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in recent years: advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation patients treated with EGFR-TKI compared with that of the patients treated with chemotherapy, the objective response rate (ORR) and progression-free survival (PFS) signiifcantly increased, the quality of life improved, both in ifrst- or second-line therapy; gene mutation status should be made clear as early as possible, even for chemotherapy-treated patients, genetic testing is also very necessary; hTere are studies show that EGFR-TKI treat patients with EGFR mutations, the response rate and disease control rate in chemonaive patients are higher than those in chemotherapy-treated patients, however, there is no difference in PFS and OS.

  11. Study on the Clinical Value of Epidermal Growth Factor Receptor Muta-tions in the Targeted Therapy for Advanced Non-small Cell Lung Cancer%表皮生长因子受体突变在晚期非小细胞肺癌靶向治疗中的临床价值研究

    Institute of Scientific and Technical Information of China (English)

    肖琳; 李代强; 赵帅

    2014-01-01

    Objective To discuss the feasibility of targeted therapy represented by epidermal growth factor receptor (EGFR) tyro-sine kinase inhibitor getfinibi for advanced non-small cell lung cancer (NSCLC). Methods 32 cases with advanced NSCLC failed the previous platinum based chemotherapy from March 2011 to October 2013 were selected and treated by getfinibi 250 mg/d. RECIST criteria were used to evaluate the curative effect. And the EGFR tyrosine kinase domain gene mutation in the tumor tissue of the patients with getfinibi treatment was detected. Results Of the 32 cases of specimens, there were 12 cases were detected with gene mutations, including 4 cases with chromosome 19 deletion mutation, 8 cases with missense mutation of chromosome 21, all were L858R mutations (T>G). After treatment with getfinibi, the objective response rate of the EGFR gene mutation group reached 58.33%, the disease control rate reached 100.0%, higher than 10.00%, 20.00%of the non-EGFR gene mutation group, respective-ly(PG)。经getfinibi治疗后EGFR基因突变组的客观有效率达58.33%,疾病控制率达100.0%,均高于无EGFR基因突变组(分别为10.00%、20.00%)(P<0.05)。结论 getfinibi靶向治疗晚期 NSCLC 疗效明显,getfinibi治疗效果明显的患者中EGFR基因突变的发生率高,因此,EGFR酪氨酸激酶域突变检测可作为患者应用getfinibi疗效的一个预测指标。

  12. Docetaxel as salvage chemotherapy in patients with advanced non-small cell lung cancer after failure of cytotoxic agents and gefitinib treatment%晚期非小细胞肺癌化疗和靶向治疗失败后的挽救性化疗

    Institute of Scientific and Technical Information of China (English)

    Yilong Wu; Jinji Yang; Yujuan Huang; Qin Zhou; Yisheng Huang; Chongrui Xu

    2008-01-01

    Objective:We conducted a prospective phase Ⅱ trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer (NSCLC) after failure of chemotherapy and gefitinib to assess the efficacy and toxicity of docetaxel in this setting.Methods:Patients with histologically confirmed NSCLC who were failure of chemotherapy and gefitinib were given docetaxel 75 mg/m2 intravenously for 30 min every 3 weeks until the toxicity was unacceptable or disease progressed.The response evaluation criteria in solid tumors (RECIST) guidelines were used for the evaluation of antitumor activity.Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 2.0.Results:In total,31 patients were enrolled in this phase Ⅱ trial between February 2004 and December 2006,and 84 cycles (average 2.7 cycles) were given.We observed 4 partial responses (PRs) and 10 stable disease (SD) states in 31 eligible patients.The objective response rate was 12.9%,and the disease control rate was 45.2%.The median survival time (MST) was 10 months (95% Cl,5.05-15.08 months).The 1-year survival rate was 40.6%.The most common toxicities were neutropenia,anemia,and peripheral neuropathy that occurred as follows:45% of the patients experienced grade 3 or 4 neutropenia,29% experienced grade 3 anemia,and 25.8% had grade 3 peripheral neuropathy.No patient terminated docetaxel chemotherapy due to toxicity.Conclusion:Docetaxei is beneficial as salvage chemotherapy in patients with advanced NSCLC after failure of cytotoxic agents and gefitinib.

  13. Influence of comorbidity on the choice of treatment and survival of elderly patients with advanced non-small cell lung cancer%合并症对老年晚期NSCLC患者治疗和生存期的影响

    Institute of Scientific and Technical Information of China (English)

    Aiwu Li; Caicun Zhou; Jianfang Xu; Ren Zhu; Jie Luo; Shanhao Chen

    2008-01-01

    Objective:To identify the influence of comorbidity on the choice of treatment and survival of elderly patients (≥70 years) with advanced non-small cell lung cancer (NSCLC).Methods:The clinical characteristics and the choices of treatment of 177 elderly patients,who had a good performance status (PS<1) were retrospectively analyzed in Oncology Department,Shanghai Pulmonary Hospital,between January 2005 to December 2005.Survival data were only analyzed in those whose had received chemotherapy.All patients were stratified by number of comorbidity as none (0),mild (1-2) and severe (≥3) groups.Results:The proportion of patients,who received chemotherapy,with none,mild and severe comorbidity was significantly different (79.3%,76.2% and 57.4%,P=0.038),and there was also significantly different about palliative radiotherapy rate among the three groups (21 1%,11.7% and 37.0%,P=0.014).The median survival and 1-year survival rate in none,mild and severe comorbidity groups,were 13.6 vs.10.2 vs.7.6 months and 53.5% vs.41.3% vs.20.8% respectively (Log-rank,P=0.071).In univadate and multivariate Cox models analysis,only severe comorbidity was a independent hazard factor of survival of elderly patients with NSCLC.Relative ratio (RR,95% Cl):(2.09,1.06-4.15),P=0.034.Conclusion:Comorbidity may affect the choice of treatment of elderly patients with advanced NSCLC slightly,but only severe comorbidity is a independent prognostic factor of survival.

  14. 热疗联合化疗治疗晚期非小细胞肺癌伴神经内分泌化的临床研究%Clinical study of thermotherapy with chemotherapy in advanced non-small cell lung cancer with neuroendocrine differentiation

    Institute of Scientific and Technical Information of China (English)

    王勇; 张延顺

    2014-01-01

    Objective To study the clinical efficacy of thermotherapy combined chemotherapy in the treatment of the advanced non-small cell lung carcinoma with neuroendocrine differentiation (NSCLC-NED).Methods The clinical data of 16 patients with NSCLC-NED were retrospectively reviewed.To analyzed the efficacy and survival of these patients.All patients were treated by thermotherapy with the combined chemotherapy regiment of platinum agents.Results There were 7 partial responses and 4 stable disease,The overall response rate (RR) was 43.8%.The one year survival rate was 37.5% (6/16).The improvement rate of quality of life was 62.5% (10/16).Conclusion Neuroendocrine differentiation is an important indicator of biological behavior of NSCLC.Thermochemotherapy is an active regimen in the advanced NSCLC-NED with an acceptabe toxicity.%目的 探讨热疗联合化疗治疗晚期非小细胞肺癌伴神经内分泌化(NSCLC-NED)的临床疗效.方法 回顾性分析16例NSCLC-NED患者的临床资料,所有患者接受含铂类联合方案化疗,同时给予局部热疗,随访其疗效及生存情况.结果 16例患者中部分缓解(PR)7例,稳定(SD)4例,近期有效率(RR)43.8%,1年生存率为37.5% (6/16),生活质量改善率62.5% (10/16).结论 神经内分泌分化是NSCLC生物学行为的重要指标,化疗联合热疗安全、有效.

  15. 含奈达铂与含顺铂化疗方案对晚期非小细胞肺癌疗效与不良反应比较的Meta分析%Meta-analysis of comparing nedaplatin-containing chemotherapy with cisplatin-containing chemotherapy in the treatment of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    罗龙; 周天骏; 姚和瑞

    2012-01-01

    目的 系统评价和比较含奈达铂或顺铂的化疗方案在晚期非小细胞化疗中的疗效、不良反应等.方法 在Medline、Embase、Cochrane图书馆、临床试验注册库、中国医院数字化图书馆、万方、维普数据库和美国及欧洲临床肿瘤学历年会议中检索有关晚期非小细胞肺癌患者使用奈达铂或顺铂方案化疗对比的随机临床试验,按Meta分析软件(RevMan 5.1)要求处理有关数据.结果入选6篇文献,试验组与对照组分别为380例与362例.含奈达铂与含顺铂方案相比,客观有效率无统计学差异[OR=1.03,95% CI(0.75,1.41),P=0.84],而Ⅲ~Ⅳ级恶心、呕吐发生率明显降低[OR=0.22,95% CI(0.14,0.324),P<0.00001],肾脏毒性发生率明显降低[OR=0.41,95% CI(0.22,0.75),P=0.004].血液性毒性较顺铂组高[OR=1.34,95% CI(1.00,1.80),P=0.05].结论 奈达铂与顺铂相比在客观有效率方面无统计学差异,恶心、呕吐、肾脏毒性的反应较顺铂明显降低,而血液性毒性较顺铂组高.有希望成为顺铂的替代方案.然而远期生存率等指标比较尚需进一步大规模的临床试验证实.%Objective To invesligale the efficacy and side effect of nedaplalin and cisplalin in the treatment of advanced non-small cell lung cancer. Methods To search all of randomized controlled Lrials on chemotherapy containing nedaplalin or cisplalin in the trealmenl of advanced non-small cell lung cancer in Medline, Embase, Cochrane library,Clinical trials, CHKD, Wanfang database, VIP informalion and the data of American and Europe cancer conferences. A Mela-analysis was carried out by RevMan 5. 1. Results Six sellings with 380 palienls in study group and 362 palienls in conltrol group were selected. There was no slalislical difference between the sludy group ( containing nedaplatin) and the control group( containing cisplalin) in objective response rale[ OR = 1. 03 ,95% CI (0. 75,1.41),P = 0.84]. The nausea and vomiting rate [ OR

  16. 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

  17. Clinical efficacy of docetaxel plus cisplatin regimen and gemcitabine plus cisplatin regimen in first-line chemotherapy for the treatment of advanced non-small cell lung cancer%多西他赛与吉西他滨分别联合顺铂治疗晚期非小细胞肺癌的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘爱学; 李明淑; 周泽强; 张容榕; 金花; 冯天举; 谭淑瑜; 李美香; 林琳

    2013-01-01

    Objective To compare the therapeutic effects and toxic reactions of DP regimen (docetaxel plus cisplatin) and GP regimen (gemcitabine plus cisplatin) in the treatment of advanced stage non-small cell lung career (NSCLC). Methods A total of 79 patients with advanced stage NSCLC were treated by first-line chemotherapy for 4~6 weeks. The patients were divided into two groups: DP group (docetaxel plus cisplatin) and GP group (gemcitabine plus cisplatin). Patients in DP group (n=43) were treated by 75 mg/m2 docetaxel on day 1 plus 25 mg/m2 cisplatin on day I to day 3. Patients in GP group (n=36) were treated by 1000 mg/m2 gemcitabine on day 1 and day 8 plus 25 mg/m2 cisphtin on day 1 to day 3. Twenty-one days were a treatment cycle. The treatment response rate and survival rate were evaluated by the end of every two cycles. Results The response rate was 37.21% for DP group and 33.33% for GP group, with no statistically significant difference between the two groups (P>0.05). The response rate also had no statistically significant difference in adenocarcinoma and squamous carcinoma sub-groups. The main side effects were myelosup-pression, nausea and omiting. There was no statistically significant difference in Ⅲ ~Ⅳ grade thrombocytopenia and gastrointestinal side effects between the two groups. Conclusion Both DP regimen (docetaxel and cisplatin) and GP regimen (gemcitabine and cisplatin) in first-line chemotherapy have good therapeutic effects and toleranted toxic reactions in the treatment of advanced stage non-small cell lung cancer (NSCLC).%目的 比较多西他赛联合顺铂与吉西他滨联合顺铂一线治疗晚期非小细胞肺癌的疗效和不良反应.方法 晚期非小细胞肺癌患者79例,均接受4~6周期一线化疗.多西他赛联合顺铂组(DP组)43例:多西他赛75 mg/m2,第1天,顺铂25 mg/m2,第1~3天.吉西他滨联合顺铂组(GP组)36例:吉西他滨1 000 mg/m2,第1天、第8天,顺铂用量同DP组.21d为一个化疗周期,每2

  18. Ph 1 Study in Subjects With Tumors Requiring Arginine to Assess ADI-PEG 20 With Pemetrexed and Cisplatin

    Science.gov (United States)

    2016-08-10

    Pleural Mesothelioma Malignant Advanced; Peritoneal Mesothelioma Malignant Advanced; Non-squamous Non-small Cell Lung Carcinoma Stage IIIB/IV (NSCLC); Metastatic Uveal Melanoma; Hepatocellular Carcinoma (HCC); Glioma; Sarcomatoid Cancers

  19. Anaplastic lymphoma kinase (ALK inhibitors for second-line therapy of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Berghmans T

    2012-12-01

    Full Text Available Thierry Berghmans,1 Myriam Remmelink,2 Ahmad Awada31Clinic of Thoracic Oncology and Department of Intensive Care, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; 2Department of Pathology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; 3Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, BelgiumAbstract: Targeted therapies are nowadays a treatment option in metastatic non-small cell lung cancer, for which oncogenic drivers have been identified. The epidermal growth factor-receptor tyrosine kinase inhibitors gefitinib and erlotinib, are the standard of care for patients in whom tumors are presenting with an activating epidermal growth factor-receptor mutation, with new active agents like afatinib reaching clinics in the near future. Other genetic abnormalities have been documented in squamous and non-squamous lung cancer. The EML4–ALK gene fusion is a rare event, occurring in around 5% of lung cancer, quite exclusively in adenocarcinoma with a predominance of young non/light smokers. Detection of ALK-positive tumors is challenging, as there is no gold-standard technique. Fluorescence in situ hybridization is the method used in prospective trials assessing the activity of crizotinib and is recommended by the American FDA. Crizotinib is the first orally active inhibitor of receptor tyrosine kinases, including ALK and ROS1, in clinical practice. Impressive results came from a phase I study and are now confirmed in a large phase II study with response rate of 60%, whatever the number of previous lines of chemotherapy. Other ALK inhibitors are currently in the preclinical phase, and some are showing promising results in early phase I/II studies. This review aims to present the current knowledge on the EML4–ALK gene fusion, the pitfalls for the pathologist and the clinician in searching this abnormality, and to review the existing literature on ALK inhibitors under

  20. 厄洛替尼治疗晚期非小细胞肺癌近期疗效和安全性研究%Study on the short -term efficacy and safety of erlotinib in treatment of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    尤青海; 张丹; 牛成成

    2012-01-01

    Objective To evaluate the short-term efficacy and safety of erlotinib on advanced non-small lung cell cancer ( NSCLC). Methods Twenty-one patients with advanced NSCLC ( Hlb/IVstage) , who failed to prior chemotherapy, were enrolled in the study. Erlotinib (ISO nig) was orally administered daily. Restults There were zero patients who got complete remission, seven patients who got partial remission and six patients whose condition was stable in total patients. Therefore, the objective remission rate is 33. 3% and the disease control rate is 61. 9%. The disease control rate of the female is prior to the male in the treatment efficacy of erlotinib (P 0. 05 ). The major adverse reactions of erlotinib were shin rash with the incidence of 80% and diarrhea with the incidence of 42. 9% , which were mostly in I / II degree. Conclusion Erlotinib is effective in treatment of advanced NSCLC with minor adverse reactions and its treatment efficacy in the female is prior to that in the male.%目的 评价厄洛替尼治疗晚期非小细胞肺癌(NSCLC)的近期疗效.方法 21例确证的化疗失败的Ⅲb/Ⅳ期NSCLC患者入组,给予厄洛替尼150mg/d口服,直至疾病进展,观察近期疗效和不良反应.结果 21例患者中完全缓解0例,部分缓解7例,客观缓解率为33.3%;稳定6例,疾病控制率为61.9%;女性疾病控制率优于男性(P<0.05),而吸烟、肿瘤类型、皮疹及腹泻均与客观缓解率和疾病控制率无关(P>0.05);主要毒副反应为1/2度皮疹和腹泻,发生率分别为80%和42.9%.结论 厄洛替尼能有效治疗晚期NSCLC,女性疗效更佳,且不良反应少.

  1. Clinical study of TP and GP in treating advanced non-small cell lung cancer%吉西他滨联合顺铂与紫杉醇联合顺铂治疗晚期非小细胞肺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    王心玲; 李红; 王大本; 张玉梅

    2009-01-01

    Objective To investigate the efficacy and toxicity of the GP regimen and TP regimen on advanced non-small cell lung cancer(NSCLC).Methods Sixty-six advanced NSCLC patients were randomly divided into two groups.34 in GP group and 32 in TP group.GP group:gemeitabine 1000 ms/m2,d1、d8;cisplatin 30 ms/m2,d1~3.TP group:paclitaxel 135 ms/m2,d1;cisplatin 30 ms/m2,d1~3.The efficacy and side effects were analyzed after two cycles of chemotherapy.Results The short term effective rate for Mvanced NSCLC in GP group andTP group was41.2%(14/34)and 40.6%(13/32),110 significant statistical difference was found between the two groups(P>0.05).In the adverse effects of treatment,the major cytotoxicity was thrombocytopenia in GP group and leukopenia in TP group but they were tolerable.Conclusion The curative effect of GP regimen and TP regimen are affirmed.there are certain differences in adverse reactions.Different themes can be chosen according to different choices in patients with Mvanced non=small cell lung cancer.%目的 探讨吉西他滨联合顺铂(GP)方案和紫杉醇联合顺铂(TP)方案对初治的晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法 66例初治晚期NSCLC患者随机分为GP组(34例)和TP组(32例).GP组:吉西他滨1000 ms/m2,第1、8天;顺铂30 ms/m2,第1~3天.TP组:紫杉醇135 mg/m2,第1天;顺铂30 ms/m2,第1~3天.化疗2个周期后对两组的临床疗效和不良反应进行评价.结果 GP和TP两组的有效率分别为41.2%(14/34)和40.6%(13/32).两组资料比较差异无统计学意义.GP组以血小板降低为主,TP组以白细胞降低为主,均在可耐受范围内.结论 GP方案和TP方案对晚期NSCLC疗效肯定,不良反应有一定差异,可根据不同个体选用不同的化疗方案.

  2. A Case Study of Locally Advanced Non-small Cell Lung Cancer with Severe Mixed Infections:Differential Diagnosis and Treatment%局部晚期非小细胞肺癌合并重症混合性感染个案分析

    Institute of Scientific and Technical Information of China (English)

    赵晓亮; 林丽; 陈玉龙; 肖建宇; 王长利

    2012-01-01

    局部晚期非小细胞肺癌患者由于病情复杂及自身状况较差,是重症或混合性感染高发人群,主要原因为多存有重症感染的高危因素,包括长期吸烟史、常罹患糖尿病、慢性阻塞性肺病,肺阻塞及膨胀不良等造成肺部自洁功能下降,以及外科手术、放疗、化疗等相关治疗和药物对机体造成的免疫抑制等.肺癌合并重症感染临床表现多样,原因机制复杂,病情进展迅速,预后差.临床治疗上缺乏完善的疗效评价体系,存在临床及影像学上变化不同步,同时需与多种疾病相鉴别.现介绍天津医科大学附属肿瘤医院肺部肿瘤科2011年3月收治的1例经多学科综合治疗的局部晚期非小细胞肺癌合并重症混合性感染的病例.该患者化疗过程中出现重症混合性肺感染,经综合治疗后效果较佳.同时探讨肺癌合并重症混合性感染的鉴别诊断和治疗规范.%Patients with locally advanced non-small cell lung cancer are high-risk populations who usually suffer from severe or mixed infections because of their complex body conditions. The main causes of severe infections in patients with high risk factors include smoking history, diabetes, chronic obstructive pulmonary disease, and pulmonary congestion and swelling caused by the decline in lung self-cleaning functions. Other possible causes include surgical operations, radiotherapy, chemotherapy, and other treatments and medications that can result in the immunosuppressive state. Lung cancers complicated with severe infections have diverse clinical manifestations, result in complex mechanisms and rapid disease progression, and have poor prognosis. The lack of an effective evaluation system for clinical treatment and the changes in the clinical and radiographic fields are not synchronous with the wide variety of disease differentiation. The current report presents one case of a locally advanced non-small cell lung cancer complicated with a severe

  3. Progress on epidermal growth factor receptor tyrosine kinase inhibitor for treatment of advanced non-small cell lung cancer%表皮生长因子受体酪氨酸激酶抑制剂治疗晚期非小细胞肺癌研究进展

    Institute of Scientific and Technical Information of China (English)

    陈佳艳; 周彩存

    2011-01-01

    表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)已成为晚期非小细胞肺癌治疗的研究热点.在有EGFR突变的患者中,一线单药EGFR-TKI能显著延长患者无进展生存期;EGFR突变是EGFR-TKI治疗获益的有效预测指标.虽然EGFR-TKI与化疗同步联合未能显示出生存优势,但在序贯联合的研究中能延长无进展生存期.EGFR-TKI维持治疗能显著延长无进展生存期.EGFR-TKI二线治疗较安慰剂有显著生存获益,与标准二线治疗总生存期相似,但安全性更好.%Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been the focus of clinical trials for treatment of advanced non-small cell lung cancer. In patients with EGFR mutation, first-line EGFR-TKI monotherapy can significantly improve progression-free survival. EGFR mutation is an effective predictor of benefit treatment. Although the use of EGFR-TKI in combination with chemotherapy fails to show a survival advantage,progression-free survival can be prolonged in the sequential study. EGFR-TKI maintenance treatment can significantly prolong progression-free survival. Second-line treatment of EGFR-TKI shows significant survival benefit compared with placebo, has similar overall survival with the standard second-line treatment, but better security.

  4. Advances in Liquid Biopsy and its Clinical Application in the Diagnosis and Treatment of Non-small Cell Lung Cancer%液体活检及其在非小细胞肺癌诊治中的研究进展

    Institute of Scientific and Technical Information of China (English)

    郑迪凡; 陈海泉

    2016-01-01

    With the advances of technology, great progresses have been made in liquid biopsy in recent years. Liquid biopsy is currently playing a more and more important role in early diagnosis and treatment of cancer. Compared with traditional tissue biopsy, liquid biopsy is more popular in clinical practice due to its non-invasiveness, convenience and high repeatability. It has huge potential in the future. hTis review introduces circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) as the most important objects in liquid biopsy, mainly focusing on their history, biological characteristics, de-tection technologies, limitations and applications in non-small cell lung cancer.%随着近几年科学技术的进步,液体活检技术也有了长足的发展,并在肿瘤的早期诊断及后期治疗中扮演着越来越重要的角色。相比于传统的组织活检,液体活检以其独有的无创性、便捷性、高重复性等特点在临床上得到更多的青睐,在未来有着巨大的发展潜力。本文重点探讨了循环肿瘤细胞(circulating tumor cells, CTCs)和循环肿瘤DNA(circulating tumor DNA, ctDNA),作为液体活检最重要的两个检测对象,其历史、生物学特性,检测手段,局限性及其在非小细胞肺癌诊治中的应用。

  5. 紫龙金片治疗晚期非小细胞肺癌患者化疗后感染的临床观察%Clinical effect of Zilongjin tablets on treatment of advanced non-small cell lung cancer complicated with infections after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    孙彩萍; 陈遐林; 朱晓灵; 叶万立; 刘秋霞; 王建芳

    2014-01-01

    目的:探讨紫龙金片治疗晚期非小细胞肺癌化疗后合并感染的临床效果,为合理使用抗菌药物提供依据。方法回顾性分析晚期非小细胞肺癌患者化疗后发生医院感染的72例患者的临床资料,并观察采用紫龙金片治疗的临床效果。结果273例治疗患者中发生感染72例,感染率为26.4%;单部位感染68例占94.4%,多部位感染4例占5.6%;感染高发部位以呼吸系统及消化系统为主,分别占72.0%和19.5%;72例感染患者中化疗1次占15.3%、2次占34.7%、≥3次占50.0%;共检出病原菌68株,其中革兰阳性菌22株占32.3%,革兰阴性菌38株占55.9%,真菌8株占11.8%;感染控制65例,占90.3%,死亡3例,病死率4.1%,自动出院4例。结论晚期非小细胞肺癌化疗后感染时,应在药敏结果的指导下合理使用抗菌药物药物治疗,同时防止真菌感染的发生,合理使用粒细胞集落刺激因子,并加强营养支持治疗。%OBJECTIVE To explore the clinical effect of Zilongjin tablets on treatment of advanced non-small cell lung caner complicated with infections after chemotherapy so as to provide guidance for reasonable use of antibiot-ics .METHODS The clinical data of 72 patients with advanced non-small cell lung cancer complicated with nosoco-mial infections were retrospectively analyzed ,then the clinical therapeutic effect of Zilongjin tablets was observed . RESULTS The infections occurred in 72 of 273 patients with the infection rate of 26 .4% ,including 68 (94 .4% ) cases of single site infections and 4 (5 .6% ) cases of multiple sites infections ;the patients with respiratory system infections accounted for 72 .0% ,the patients with digestive system infections 19 .5% .Of the 72 patients with in-fections ,15 .3% underwent the chemotherapy for once ,34 .7% for twice ,50 .0% for no less than three times .A total of 68 strains of pathogens have

  6. 三维适形放射治疗与同步化疗治疗晚期非小细胞肺癌效果比较%Three-dimensional Conformal Radiotherapy Synchronized with Chemotherapy for Patients with Locally Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    黄玉; 戈伟; 唐甜; 李长虎; 郑永法

    2013-01-01

    Objective To evaluate the efficacy and saiety of three-dimensional conformal radiation therapy synchronized with chemotherapy in patients with locally advanced non-small cell lung cancer. Methods The literature related to evaluation of the three-dimensional conformal radiation therapy plus chemotherapy for the patients with locally advanced non-small cell lung cancer were retrieved from Cochiane Database of Systematic Reviews, MEDLINE , EMbase, OpenSICLE , National Technical Information Service (NTIS) ,CNKI, VIP, Wanfang database and CBM from the day of database establishment till the October 2011. Two authors independently appraised the quality of the reference research, extracted the data, and performed Meta analysis to the RCTs which met the quality standards. The extracted data were analyzed by RevMan5. 0. 25 . Results A total of 12 trials were included. Meta analysis of five key outcome indicators showed that three-dimensional conformal radiation therapy with concurrent chemotherapy had significantly improved the treatment efficiency and local symptoms [OR = 2.52, 95% CI (1.41,4.52) and OR = 3.22,95% CI (1. 32,7. 83) respectively]. But, no conspicuously difference was found in radiation esophagitis, radiation pneumonitis and bone marrow suppression degree. Conclusion The current evidence shows that three-dimensional conformal radiotherapy combined with chemotherapy can significantly improve local symptoms and treatment efficiency in patients with locally advanced non-small cell lung cancer, and most patients can tolerate the side effects, clinicians may recommend the combination therapy over radiation alone. Due to the limitations of the included studies, more large-scale, high-quality RCTs are required.%目的 系统评价单纯三维适形放射治疗(放疗)与同步化学治疗(化疗)在局部晚期非小细胞肺癌治疗中的疗效与安全性.方法计算机检索Cochrane Database of Systematic Reviews

  7. Efficacy analysis of stereotactic body radiation therapy combined with chemotherapy for locally advanced non-small cell lung cancer%体部立体定向放射治疗联合化疗治疗局部晚期非小细胞型肺癌疗效分析

    Institute of Scientific and Technical Information of China (English)

    李崇国; 李昌林; 唐汉军

    2012-01-01

    目的 评价体部立体定向放射治疗联合化疗治疗不能手术或拒绝手术的局部晚期(WHO分期ⅢA、ⅢB)非小细胞肺癌的疗效和不良反应.方法 将2006年8月~ 2009年2月期间,我院治疗的110例符合入选条件的局部晚期非小细胞肺癌患者随机分成治疗组和对照组.治疗组:体部立体定向放射治疗联合化疗.体部立体定向放射治疗:单次处方剂量50%等剂量曲线为350cGy~400cGy,1/d次,共12~14次,总剂量49Gy~56Gy.化疗:采用紫杉醇+顺铂方案,于体部立体定向放射治疗治疗后1周左右开始,平均4个周期.对照组:常规放射治疗联合化疗.采用60Co体外照射,放射剂量为50Gy~54Gy,180cGy ~200cGy/次,每周5次,5~6周完成.化疗方案同治疗组.结果 治疗组有效率、1年、2年生存率和放射性肺炎发生率分别为81.94%、65.28%、47.22%、3.57%.对照组:有效率、1年、2年生存率和放射性肺炎发生率分别为63.16%、39.47%、23.68%、16.67%.结论 体部立体定向放射治疗联合化疗对不能手术或拒绝手术的局部晚期NSCLC有效,不良反应轻微.%Objective This study evaluated the efficacy and side effects of stereotactic body radiation therapy (SBRT) combined with chemotherapy in the treatment for inoperable or refused surgery locally advanced ( World Health Organization stage Ⅲ A、ⅢB) non-small cell lung cancer patients. Methods From August 2006 to February 2009,110 patients with locally advanced non-small cell lung cancer were randomly divided into Treatment Group and Control Group in this study. Treatment Group: SBRT combined with chemotherapy. SBRT with schema-periphery dose 350cGy ~400cGy per fraction (50% dose line) ,12 ~ 14 fractions was carried out, at a total dose of 49Gy ~ 56Gy. Chemotherapy with TP regimen 4 cycles was performed one week after SBRT. Control Group: Conventional radiotherapy combined with chemotherapy, dose 180cGy ~ 200cGy per fraction

  8. 紫杉醇+卡铂及吉西他滨+卡铂方案治疗晚期非小细胞肺癌的临床观察%Clinical efficacy and adverse effects of taxel plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    王晓云; 赵玉亮

    2010-01-01

    Objective To observe the clinical efficacy and adverse effects of taxel plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. Methods 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: taxel 150 mg/m2, d1, carboplatin 300 mg/m2 in d1; GP group:gemcitabine 1000 mg/m2, 30 min, d1, 8, carboplatin 300 mg/m2 in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. Results 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. Conclusion 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.%目的 了解紫杉醇+卡铂(TP)及吉西它滨+卡铂(GP)方案治疗晚期非小细胞肺癌的近期疗效和副作用.方法 北京大学第一医院肿瘤化疗科2003年9月至2010年8月确诊的晚期非小细胞肺癌86例,TP、GP方案治疗各43例.至少治疗2周期或以上.TP组:紫杉醇150 mg/m2,第1天;卡铂300 mg/m2,第1天,21 d为1个周期.GP组:吉西它滨1000

  9. EGFR 19与21号外显子突变的晚期非小细胞肺癌一线TKI治疗疗效差异的研究进展%Research Advance on Difference of Efficacy of First-line Tyrosine Kinase Inhibitor Treatment for Advanced Non-small Cell Lung Cancer Patients with Exon 19 and 21 EGFR Mutation

    Institute of Scientific and Technical Information of China (English)

    冯佳; 许斌

    2016-01-01

    表皮生长因子受体(epidermal growth factor receptor,EGFR)19号外显子缺失和21号外显子的L858R点突变是非小细胞肺癌(non-small cell lung cancer,NSCLC)中最常见的EGFR突变类型,并且预示经EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗给患者带来更优的生存获益.临床研究表明,这两种突变类型患者在EGFR-TKI治疗中的获益有差异.文章主要就EGFR 19与21号外显子突变的晚期NSCLC一线TKI治疗疗效差异的研究进展作一综述.

  10. Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Boutsikou E

    2013-03-01

    Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

  11. 抗抑郁治疗对晚期非小细胞肺癌患者生活质量和化疗疗效的影响%Antidepressant Therapy Improves Quality of Life and Chemotherapeutic Efficacy in Patients with Advanced Non-Small-Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    陈颖兰; 刘震天; 万莉娟; 邹俊韬

    2015-01-01

    ABSTRACT:Objective To compare the effects of conventional chemotherapy and conventional chemotherapy combined with antidepressant therapy on the quality of life and chemotherapeutic efficacy in patients with advanced non-small-cell lung cancer(NSCLC).Methods Patients meet-ing inclusion criteria were randomly treated with conventional chemotherapy alone(control group) or in combination with antidepressant therapy(treatment group).Before,during and after treat-ment,the performance status,depression and chemotherapeutic efficacy were assessed using Karnofsky Performance Status Scale (KPS),Zung Self-Rating Depression Scale (SDS)and Re-sponse Evaluation Criteria in Solid Tumors(RECIST),respectively.Results Compared with con-trol group,KPS score was increased and chemotherapeutic efficacy was improved in treatment group during and after treatment(P<0.05).Conclusion Antidepressant therapy can improves the quality of life and chemotherapeutic efficacy in patients with advanced NSCLC.%目的:探讨晚期非小细胞肺癌患者常规化疗与常规化疗联合抗抑郁治疗生活质量、化疗疗效的差异。方法将符合纳入标准的39例患者按简单随机方法分为治疗组(19例)和对照组(20例),治疗组给予常规化疗加抗抑郁治疗,对照组仅给予常规化疗,所有患者在治疗前、中、后给予卡式评分及抑郁评估,采用 Karnofsky 功能状态量表(KPS)进行行为状态评估,采用Zung抑郁自评量表(SDS)进行抑郁评估,同时采用 WHO实体瘤疗效评估标准进行化疗疗效评价。结果治疗组治疗中及治疗后的KPS评分高于对照组(P<0.05),且治疗组化疗疗效优于对照组(P<0.05)。结论抗抑郁治疗可提高晚期肺癌患者生活质量和化疗疗效。

  12. Clinical Observation of Thermotherapy Combined with TP Chemotherapy in Treating Advanced Non-small Cell Lung Cancer%热疗联合TP方案化疗治疗中晚期非小细胞肺癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    陈维; 魏涛; 陈林

    2014-01-01

    目的:探讨热疗联合TP方案化疗治疗中晚期非小细胞肺癌(NSCLC)的临床疗效、生活质量改善率和毒副反应。方法40例入组的ⅢB期或Ⅳ期NSCLC患者,随机分为对照组(20例)和治疗组(20例),治疗组采用热疗联合TP方案化疗2周期,对照组仅行TP方案化疗2周期,比较两组间临床疗效、生活质量改善及毒副反应的差异。结果治疗组和对照组的有效率分别为65%和35%,差异有统计学意义(P<0.05);两组患者间生活质量改善率的差异有统计学意义(P<0.05);两组间毒副反应的差异无统计学意义(P>0.05)。结论热疗联合化疗治疗中晚期NSCLC疗效确切,生活质量明显改善,毒副反应可以耐受,值得临床推广应用。%Objective To investigate the clinical efifcacy, the change of KPS scores and side effects induced by thermotherapy combined with TP chemotherapy in treating patients with advanced non-small cell lung cancer(NSCLC).Methods Forty cases with NSCLC stageⅢB orⅣ were enrolled in this study, they were randomly divided into two groups. The observation group (n=20) was treated with paclitaxel plus cisplatin (TP) for two cycles, combined with thermotherapy. The control group (n=20) was treated only with regular TP chemotherapy for two cycles. The clinical efifcacy, the change of karnofsky (KPS) scores and side effects were compared between the two groups.Results The response rate in observation group was 65%, and 35% in control group. There was signiifcant difference between two groups (P0.05).Conclusion Thermotherapy combined with TP chemotherapy can increase efifcacy and improve life quality of the patients with advanced NSCLC, and the toxicity can be tolerated, it was worthy for clinical use.

  13. Intensity-modulated radiotherapy combined with gemcitabine and cisplatin chemotherapy for local advanced non-small cell lung cancer%调强放疗联合吉西他滨加顺铂治疗局部晚期非小细胞肺癌临床观察

    Institute of Scientific and Technical Information of China (English)

    饶建

    2015-01-01

    目的 观察调强放射治疗联合吉西他滨、顺铂同步化疗治疗局部晚期非小细胞肺癌疗效与安全性.方法 回顾分析2012年1月至2014年6月在我院肿瘤科行调强放疗的45例局部晚期NSCLC患者.给予调强放疗,处方剂量为PTV 50.4 Gy/28次,常规分割,同步GTV推量,PTV-GTV为60 Gy/28次.同步给予化疗,方案为吉西他滨加顺铂,方案为放疗第1d起开始化疗,吉西他滨1.0 g/m2,dl、d8,顺铂25 mg/m2,dl ~3,每21d重复.放疗后再采用该方案化疗4个周期.主要观察指标为总有效率(ORR)、毒副反应.结果 所有患者按计划完成治疗.近期疗效CR 6例,PR 26例,SD 12例,PD 1例.ORR 71.1%.毒副反应主要为恶心、呕吐、骨髓抑制,放射性食管炎,放射性肺炎.结论 调强放疗联合吉西他滨加顺铂同步化疗治疗局部晚期NSCLC近期疗效好,毒副反应可耐受,长期疗效有待进一步随访研究.%Objective To evaluate the clinical efficacy and toxicities of intensity-modulated radiotherapy(IMRT) combined with gemcitabine and cisplatin chemotherapy for patients with locally advanced non-small cell lung cancer(NSCLC).Method Forty five patients with NSCLC who received IMRT from January,2012 to June,2014 in our hospital were retrospectively analyzed.The IMRT plans were designed to deliver 50.4G y/28 f to PTV while delivering 60 Gy/28 f to GTV.Chemotherapy was given from the first day of IMRT,with gemcitabine 1.0 g/m2 on day l to day 8 and cisplatin 25my/m2 on day 1 to day 3.The chemothtrapy was repeated every 21 days,with a total of 4 cycles.The endpoints were overall response rate(ORR) and adverse events.Results All patients completed definitive IMRT and chemotherapy.Complete response(CR),partial response(PR),stable disease(SD),and progressive disease(PD)were observed in 6,26,12,and 1 cases,respectively,with a ORR of 71.1%.The main toxicities were tolerable,which included myelosuppression,nausea,vomiting,acute radiation pneumonia,and acute

  14. Gefitinib-induced disseminated intravascular coagulation in a patient with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    YUAN Guang-jin; KE Qin-hua; XU Xi-ming; YANG Ji-yuan; SU Xiao-yan

    2010-01-01

    @@ In February 2005, Gefitinib (Iressa), a small-molecular epidermal growth factor receptor and tyrosine kinase inhibitor, was approved in China as an anticancer agent for patients with advanced (local or metastatic) non-small cell lung cancer (NSCLC), who failed prior chemotherapy. The common adverse events of the drug include acne-like skin rash, paronychia, pruritus, diarrhea, nausea/vomiting, anorexia, hepatitis, and hyperbilirubinemia.~1

  15. Pemetrexed safety and pharmacokinetics in patients with third-space fluid

    DEFF Research Database (Denmark)

    Dickgreber, Nicolas J; Sørensen, Jens Benn; Paz-Ares, Luis G;

    2010-01-01

    Pemetrexed is established as first-line treatment with cisplatin for malignant pleural mesothelioma and advanced nonsquamous non-small-cell lung cancer (NSCLC) and as single-agent second-line treatment for nonsquamous NSCLC. Because the structure and pharmacokinetics of pemetrexed are similar to ...

  16. The efficacy of EGFR-TKI sequential chemotherapy on advanced non-small cell lung cancer after acquired resistance to EG-FR-TKI%EGFR-TKI序贯化疗对EGFR-TKI获得性耐药的中晚期非小细胞肺癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    陈咏梅; 蒋志红; 陈金云; 张燕

    2015-01-01

    Objective To explore the safety and efficacy of EGFR-TKI sequential chemotherapy on advanced non-small cell lung cancer( NSCLC) after acquired resistance to EGFR-TKI. Methods Totally 104 cases of acquired resistance to EGFR-TKI advanced NSCLC patients in our hospital were divided into EGFR-TKI sequential chemotherapy group and chemotherapy group from August 2012 to August 2013 in our hospital,with 52 cases in each group. The efficiency,incidence condition of adverse reaction and survival in 1 year of the two groups were compared. Results The chemotherapy recent total effective rate of sequential chemotherapy group was 73. 08%. It was higher than that in chemotherapy group which was 48. 08%(χ2 =6. 805,P0. 05 ) . Conclusion Patients of advanced NSCLC with EGFR-TKI treatment failure after application of EGFR-TKI sequential chemotherapy can improve patient outcomes, slow disease progression and improve long-term survival of pa-tients,and the adverse reaction is acceptable. It is advanced NSCLC EGFR-TKI get effective drug resistance after treatment strategies.%目的 探讨序贯化疗对表皮生长因子受体-酪氨酸激酶抑制剂( EGFR-TKI )获得性耐药的中晚期非小细胞肺癌( NSCLC)患者的疗效及安全性. 方法 选择2012年8月至2013年8月我院收治的104例EGFR-TKI获得性耐药的中晚期NSCLC患者作为研究对象,采用随机数字表法将患者分为EGFR-TKI序贯化疗组及单纯化疗组,每组52例患者. 对比分析1年内两组患者的疗效、不良反应发生情况及生存率. 结果 EGFR-TKI序贯化疗组患者的近期总有效率为73. 08%,显著高于单纯化疗组的48. 08%(χ2 =6. 805,P0. 05). 结论 中晚期NSCLC患者EGFR-TKI治疗失败后,应用EGFR-TKI序贯化疗可有效提高患者治疗效果,延缓病情进展,提高患者远期生存率,且不良反应可耐受,是中晚期NSCLC患者EGFR-TKI获得性耐药后的有效治疗策略.

  17. 盐酸埃克替尼治疗EGFR突变状态明确的晚期非小细胞肺癌的临床观察%Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identiifed

    Institute of Scientific and Technical Information of China (English)

    李曦; 张权; 张树才; 秦娜; 王敬慧; 杨新杰; 张新勇; 吕嘉林; 吴羽华; 张卉; 农靖颖

    2015-01-01

    背景与目的盐酸埃克替尼(icotinib hydrochloride)是我国第一个具有自主知识产权的小分子靶向抗癌新药,与吉非替尼和厄洛替尼相比,在化学结构、分子作用机理、疗效等方面相似。本研究观察盐酸埃克替尼治疗表皮生长因子受体突变状态明确的晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的疗效和毒副反应。方法回顾性分析2009年3月-2014年12月间北京胸科医院收治的晚期NSCLC患者,表皮生长因子受体(epidermal growth factor receptor,EGFR)突变状态已知,均口服盐酸埃克替尼治疗,评价其疗效和毒副反应。结果124例组织学证实的晚期NSCLC患者,其中EGFR突变型99例,野生型25例。全组客观有效率(ob-jective response rate, ORR)为51.6%,疾病控制率(disease control rate, DCR)为79.8%。突变型和野生型患者的ORR:63.6%vs 4.0%,DCR:93.9%vs 24.0%,两者均有统计学差异(P<0.000,1)。突变型和野生型患者的无进展生存期(progression-free survival,PFS)(分别为10.5个月和1.0个月)(P<0.000,1)。治疗相关的毒副反应主要为皮疹38例(30.6%),腹泻20例(16.1%)。结论盐酸埃克替尼治疗EGFR突变的晚期NSCLC疗效肯定,耐受性好。%Background and objectiveIcotinib is the ifrst 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, geiftinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the effcacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients withEGFR mutation and wild-type.MethodsPatients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March

  18. 局部晚期非小细胞肺癌的高龄患者采用全身γ刀SBRT治疗临床观察%Clinical analysis of whole body γ-knife radiotherapy for the elderly patients with locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    庞军; 陈浩涛; 陈燕; 姜林; 郝光远; 李长青

    2012-01-01

    背景与目的 体部立体定向放射疗法(stereotactic body radiation therapy,SBRT)治疗早期非小细胞肺癌(non-small cell lung cancer,NSCLC)具有较好的疗效,但对局部晚期NSCLC的治疗报道相对较少.该研究旨在探讨全身γ刀SBRT治疗高龄局部晚期NSCLC的疗效、不良反应及临床应用的可行性.方法 采用超级γ刀(SGS-Ⅰ型)治疗高龄局部晚期NSCLC患者68例,根据肿瘤的位置、临床靶体积、患者的身体状况与治疗目的,制定放射治疗计划.肿瘤体积56.9~1 097.0 cm3,等剂量曲线50%~60%,周边照射总剂量35~45 Gy,分割处方剂量3.5~5.0 Gy,重复治疗8~12次,每周5次.治疗前按定位时体位复位,再次CT扫描离线体位验证及调整计划靶体积(planned target volume,PTV)剂量分布.采用Kaplan-Meier法计算局部控制率和生存率.结果 68例患者治疗后中位随访18个月,随访率为100%.治疗结束后2~3个月经过CT复查,24例(35.29%)肿瘤消失,42例(60.29%)肿瘤缩小,2例(4.41%)无变化,总有效率为95.59%.1年局部控制率分别为61.76%.1、2、3年总生存率分别为82.35%、34.04%和20.69%.2级放射性肺炎及食管炎发生率分别为16.18%和19.12%,无2级以上放射性肺炎、食管炎的发生.PTV和验证靶区适形指数分别为0.41±0.08和0.39±0.12(t=0.09,P>0.05).结论 全身γ刀SBRT治疗局部晚期NSCLC高龄患者临床疗效确切,不良反应较轻.%Background and purpose: An definitive effect has been seen in the treatment for the patients with early stage non-small cell lung cancer (NSCLC) using body stereotactic radiotherapy, but the reports were relatively few in the patients with local advanced NSCLC. In this study, we evaluated the early effect and acute radiation reaction and the clinical application of stereotactic radiotherapy with whole body γ-knife in the elderly patients with local advanced NSCLC. Methods: From Mar. 2007 to Aug. 2010, 68 elderly patients with local advanced NSCLC

  19. Clinical Research on Staged Chinese Herbal Medicinal Therapy Combined with Chemotherapy in Treatment of Advanced Non-small Cell Lung Cancer%中医药分阶段结合化疗治疗晚期非小细胞肺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    郑欢欢

    2016-01-01

    目的:探讨中医药分阶段结合化疗治疗晚期非小细胞肺癌的临床效果。方法纳入的对象为整群选取该院自2011年1月—2013年1月所收治的77例晚期非小细胞肺癌患者,随机分为化疗组、化疗+中医组,观察治疗效果和不良反应等指标。结果(1)化疗+中医组患者临床缓解率72.50%跟化疗组67.57%相似,经χ2检验,P>0.05;(2)治疗后化疗+中医组VEGF、CEA、CYFRA21-1、KPS评分、中位生存期更佳,经t检验,P0.05 (2) After treatment, the VEGF, CEA, CYFRA21-1 and KPS scores and median survival time in the chemotherapy plus Chinese medicine group were better, P<0.05, the medi-an survival time was (10.97±2.72) months in the chemotherapy group and (14.91±2.63) months in the chemotherapy plus Chinese medicine group. (3) The incidence rates of toxic and side effects in the chemotherapy plus Chinese medicine group were obviously lower than those in the chemotherapy group, P<0.05. Nausea and vomiting occurred to 15 cases, diarrhea oc-curred to 6 cases, decrease in hemoglobin occurred to 4 cases and myelosuppression occurred to 4 cases in the chemothera-py group and nausea and vomiting occurred to 7 cases, diarrhea occurred to 2 cases, decrease in hemoglobin occurred to 2 cases and myelosuppression occurred to 2 cases in the chemotherapy plus Chinese medicine group. Conclusion The clinical effect of staged Chinese herbal medicinal therapy combined with chemotherapy in treatment of advanced non-small cell lung cancer is definite, which is worth promotion.

  20. ERCC1和XPD基因SNPs与晚期NSCLC含铂类药物化疗敏感性的关系%Association between polymorphisms of ERCC1 and XPD and sensitivity to platinum-based chemotherapy in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    张胜利; 张增利; 施敏骅

    2013-01-01

    Objective To investigate whether SNPs of ERCCKC118T) and XPD(Lys751Gln) were associated with the sensitivity of non-small-cell lung cancer ( NSCLC) to platinum-based chemotherapy in the patients with advanced NSCLC. Methods Polymorphisms of ERCC1 and XPD were detected by PCR-restrictive fragment length polymorphism (PCR-RFLP) method in 78 cases. Results No association was detected between polymorphisms of ERCC1 and XPD and age, sex, histologic type,ECOG performance status,smoking history and clinical stage of tumor. The difference of clinical response was not found among age, sex, ECOG performance status and smoking history (P>0. 05). The polymorphic genotypes of ERCCl (C118T) were related to the sensitivity to platinum-based chemotherapy. Conclusion The patients carrying at least 1 T allele(T/T+C/T) may be taken as a marker to predict the sensitivity of NSCLC to platinum-based chemotherapy.%目的 探讨切除修复交叉互补基因1(ERCC1)第118位密码子(C118T)和着色性干皮病基因D(XPD)第751位密码子(Lys751Gln)的单核苷酸多态性(SNPs)与晚期非小细胞肺癌(NSCLC)患者含铂类药物化疗疗效的关系.方法 用PCR-限制性片段长度多态性(PCR-RFLP)技术检测78例NSCLC患者的ERCC1 (C118T)和XPD(Lys751Gln)基因型.结果 ERCC1(C118T)、XPD(Lys751Gln) SNPs不受年龄、性别、吸烟史、临床分期、体力状况评分(ECOG)和病理类型影响;ERCC1 (C118T)中不同的年龄、性别、吸烟史和ECOG评分之间化疗疗效差异无统计学意义.ERCC1(C118T) SNPs与含铂类药物化疗疗效有关.结论 含有T等位基因可作为预测晚期NSCLC患者铂类药物化疗敏感性的预测指标.

  1. The Efficacy and Safety of Afatinib in the Treatment of Advanced Non-small Cell Lung Cancer Harbouring EGFR Mutations:A Systematic Review%阿法替尼治疗EGFR突变型晚期非小细胞肺癌的有效性及安全性的研究

    Institute of Scientific and Technical Information of China (English)

    罗华婷; 刘锐; 陈川; 陈晓品; 朱宇熹; 向荣

    2015-01-01

    目的:评价阿法替尼治疗EGFR突变型晚期非小细胞肺癌的有效性与安全性。方法计算机检索Cochrane图书馆、PubMed、Embase、CNKI、万方数据库。两名评价者独立评价纳入研究的质量、提取资料并交叉核对,同质研究采用RevMan 5.3软件进行meta分析,对不能合并的数据采用描述性分析。主要结局指标包括无进展生存期(Progression free survival,PFS)、总生存期(Overall survival,OS)及毒性反应。结果纳入4篇RCT,共2144例患者,EGFR突变1007例,实验组670例,对照组307例,Meta结果显示阿法替尼可显著延长EGFR突变型晚期非小细胞肺癌患者的PFS,差异有统计学意义(HR=0.49,95%CI:0.43~0.56,P<0.001),但对患者的OS(HR=1.07,95%CI:0.90~1.27,P=0.47)无明显改善。对毒性反应进行meta分析,阿法替尼组增加了患者3级以上腹泻(RR=37.19,95%CI:7.42~186.32,P<0.0001)、皮疹(RR=24.28,95%CI:6.01~98.06,P<0.00001)、便秘(RR=15.42,95%CI:3.75~63.36,P=0.0001)的发生率。结论阿法替尼可显著延长EGFR突变型晚期非小细胞肺癌的PFS,无论年龄、性别、种族、EOCG评分、突变位点及吸烟史的EGFR阳性患者均可获益,但对患者的OS无明显改善,阿法替尼增加了腹泻、皮疹及便秘的发生率,副反应相对可控,严重不良反应发生率低,安全性较高,可作为晚期非小细胞肺癌患者的一线用药选择。%Objective To review the effectiveness and safety of Afatinib in the treatment of advanced non-small cell lung cancer har-bouring EGFR mutations. Methods The Cochrane Library, Pubmed, Embase, CBM, CNKI and VIP were searched. The quality of trials was evaluated by 2 reviewers independently. The randomized controlled trials (RCTs) were analyzed by RevMan 5.3 software, and those data which cannot be merged got descriptive analysis. The outcomes included progression

  2. 非小细胞肺癌患者胸腔积液肿瘤细胞EGFR基因突变检测及其在治疗中的价值%DETECTION OF EGFR GENE MUTATIONS AND ITS CLINICAL SIGNIFICANCE IN TUMOR CELLS FROM PLEURAL EFFUSION OF ADVANCED NON-SMALL-CELL LUNG CANCER PATIENTS

    Institute of Scientific and Technical Information of China (English)

    丁丽; 张萍; 武晓楠; 程刚; 周美珍

    2011-01-01

    目的 对晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)并发恶性胸腔积液的患者利用胸腔积液中的肿瘤细胞检测表皮生长因子受体(epidermal growth factor receptor,EGFR)基因19、20及21外显子的突变,了解EGFR的突变率以及与表皮生长因子酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase factor inhibitors,EGFR-TKIs)疗效的相关性.方法 收集23例晚期NSCLC患者的恶性胸腔积液,经反复离心后取沉淀细胞行石蜡包埋,巢式PCR法扩增EGFR 19、20及21外显子,取扩增片段进行DNA测序及分析.结果 23例NSCLC患者中8例检测到EGFR基因突变,突变率为34.8%.其中4例为外显子19的缺失突变,2例为外显子21的点突变,2例患者检测到复合突变.EGFR突变在不吸烟者(7/12,58%)高于吸烟者(1/11,9%)(P<0.05),EGFR突变与性别、年龄无明显相关性.EGFR-TKIs治疗有EGFR基因突变的患者与无突变的患者相比有较高的疾病控制率(100% vs 25%,P<0.05),有突变患者的中位无疾病进展时间明显长于无突变患者(9.5月vs 2.8月),但因病例数少未能进行统计学检验.结论 恶性胸腔积液可以作为NSCLC患者进行EGFR基因突变的检测标本,胸腔积液肿瘤细胞EGFR基因突变主要位于外显子19及21,外显子19主要为缺失突变,外显子21主要为点突变.有EGFR基因突变的患者接受EGFR-TKI治疗的疗效好于无突变患者,EGFR基因突变可以作为是否接受TKI治疗的预测因子.%Objective To study the mutations m exon 19.20,and 21 of epidermal growth factor receptor( EGFR) gene in the tumor cells from pleural effusion of advanced non - small - cell lung cancer (NSCLC) and the relationship between EGFR gene mutation of cells from malignant pleural effusion (MPE) and efficacy of epidermal growth factor receptor tyrosine kinase factor inhibitors(EGFR - TKIs)in the advanced NSCLC patients. Methods Twenty - three cases of MPE from the advanced NSCLC patients

  3. Detection and Evaluation of EGFR Mutation Status in Serum of Patients with Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs%晚期NSCLC患者血清EGFR基因突变状态的测定及意义

    Institute of Scientific and Technical Information of China (English)

    马玲; 刘莉; 张涛; 单莉

    2013-01-01

    Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has shown a high response rate in the treatment of lung cancer in patients with (EGFR) mutation.The aim of this study is to evaluate the relationship between EGFR mutation status in serum and predicting benefit from EGFR-TKIs therapy in patients with advanced non-small cell lung cancer (NSCLC).Methods We examined EGFR mutation status in serum of 80 patients with advanced,EGFR-TKIs given as first-line therapy NSCLC.All patients were received long-term follow-up,and the drug efficacy were observed and evaluated.Results The EGFR mutation in serum was detected in 33.8% (27/80) of NSCLC patients examined,in which exon 19 deletion mutation was present at a frequency of 44.4% (12/27) and exon 21 point mutation was 55.6% (15/27); The response rate to EGFR-TKI in patients with EGFR mutation in serum was (55.6%,15/27),which was remarkably higher than that in EGFR wild-type patients (17.0%,9/53),the difference was statistically significant (x2=0.370,P<0.001); The median progression free survival (PFS) of patients with EGFR mutation in serum was remarkably better than that of EGFR wild-type patients (9.8 months vs 5.7 months,P=0.014).Conclusion In patients with advanced,EGFR-positive in serum NSCLC,EGFR-TKIs given as first-line therapy is associated with improved drug efficacy.The results suggest that it is feasible to use serum to detect EGFR mutation,which can predict a benefit from EGFR-TKIs given as first-line therapy.%背景与目的 小分子酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)对于表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变的肺癌患者显示出良好的治疗效果.本研究旨在探讨晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者血清EGFR基因突变状态与EGFR-TKIs疗效的关系.方法 检测80例一线口服EGFR-TKIs晚期NSCLC患者血清EGFR基因的突变状态,对患者进行

  4. Effect of Chinese Medicine Comprehensive Regimen as the Maintenance Therapy on Time to Progression and Quality of Life of Patients with Advanced Non-small-cell Lung Cancer%中医综合方案维持治疗晚期非小细胞肺癌对疾病进展时间和生活质量的影响

    Institute of Scientific and Technical Information of China (English)

    姜怡; 刘苓霜; 李春杰; 田建辉; 沈丽萍; 李和根

    2011-01-01

    目的 观察中医综合方案维持治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)对疾病进展时间(time to progression,TTP)和生活质量(quality of life,QOL)的影响.方法 采用前瞻性、随机、对照研究方法,将50例晚期NSCLC一线治疗后疾病无进展者按1∶1分为治疗组(中药制剂静脉滴注、中药汤剂口服及穴位敷贴联合应用的中医综合方案,25例)和对照组(单药维持化疗,25例),21天为1周期,治疗直至疾病进展或出现不能耐受的毒副反应或患者拒绝继续治疗.终点指标为TTP,次要指标为QOL.统计分析符合方案集,包括50例患者的TTP和43例患者2周期治疗前后的EORTC QLQ-LC43评分.结果 (1)治疗组较对照组延长TTP 23天,差异无统计学意义(87天vs64天,P=0.063);(2)治疗组患者QOL明显改善,EORTC QLQ-LC43中的各功能领域及总健康状况得分上升,各症状领域得分下降,除社会功能、认知功能、咽下困难、其他部位痛外,与对照组比较,差异均有统计学意义(P<0.05).结论 (1)中医综合方案维持治疗晚期NSCLC在延长TTP方面具有与单药维持化疗相当的疗效,在提高QOL方面更具优势.(2)需要扩大样本量进一步肯定中医药维持治疗晚期NSCLC的临床疗效.%Objective To observe the effect of Chinese medicine (CM) comprehensive regimen as the maintenance therapy (MT) on time to progression (TTP) and quality of life (QOL) of patients with advanced non-small-cell lung cancer (NSCLC). Methods The study was a prospective, randomized and controlled clinical trial. Fifty non-progressive patients with advanced NSCLC who responded to first-line therapy were randomized into the test group (25 cases, treated with CM comprehensive regimen: intravenous dripping of Chinese herbal preparation, oral administration of Chinese herbal decoction, and point application) and the control group [25 cases, treated with one of three single-agent maintenance chemotherapy regimens

  5. 体部伽玛刀序贯TP方案治疗老年局部晚期非小细胞肺癌的临床观察%Body-gamma knife sequential TP regimen for elderly patients with locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    苏加利; 易正生; 孙正良; 李学文; 范明明

    2011-01-01

    Objective To evaluate the clinical efficacy and toxicity of body-gamma knife sequential TP regimen for treatment of elderly patients with locally advanced non-small cell lung cancer( NSCLC). Methods Sixty elderly patients with locally advanced NSCLC were treated by body-gamma knife radiotherapy-, total dose from 36 to 50Gy, biological effective dose (BED) 56-75 Gy, 4-6Gy/ fraction(50% -60% dosage curve) ,3-5fractions/week. TP regimen( docetaxel 75 mg/m2 iv dj, carboplatin 300mg/m2 iv d, , 3-4 weeks was a cycle) followed 1 -2 weeks after body-gamma knife therapy. Each patient should complete no less than two cycles' chemotherapy. The response and toxicity were evaluated and survival rate was followed up. Results The total response rate was 95. 0%. The 1-, 2-and 3-year survival rate was 86. 7% , 52. 4% and 28. 3%. The main toxicities were local radiation pneumonia( 16. 7% ) , radiation esophagitis(8. 3% ) , leucopenia(75. 0% ) , and nausea/vomiting( 20. 0% ) , mainly grade 1-2. Conclusion Body-gamma knife sequential TP regimen for elderly patients with locally advanced NSCLC is effective. The toxicities are mild. It is worthy of further study.%目的 观察体部伽玛刀序贯TP方案(多西他赛+卡铂)治疗老年局部晚期非小细胞肺癌(NSCLC)的临床疗效及毒副反应.方法 60例70岁以上患者均采用体部伽玛刀放疗,50% ~ 60%处方剂量线,4~ 6Gy/次,每周3~5次,总剂量36 ~ 50Gy,生物等效剂量56~75Gy.体部伽玛刀治疗结束后1~2周序贯TP方案化疗,具体为:多西他赛75mg/m2静滴,d1;卡铂300mg/m2静滴,d1,21~28天为1周期,共化疗2~4周期.化疗结束后1个月评价疗效.结果 60例患者均完成治疗,总有效率为95.0%.1、2、3年生存率分别为86.7%、52.4%和28.3%.急性放射性肺炎发生率为16.7%,急性放射性食管炎发生率为8.3%,白细胞减少发生率为75.0%,恶心呕吐发生率为20.0%,均为1~2级.结论 体部伽玛刀序贯TP方案治疗老

  6. Influence of gross tumor volume and radiotherapy dose on prognosis of three dimensional conformal ;radiation therapy for locally advanced non-small cell lung cancer%肿瘤体积和放疗剂量对局部晚期非小细胞肺癌三维适形放疗预后的影响

    Institute of Scientific and Technical Information of China (English)

    刘兴祥

    2015-01-01

    Objective To investigate influence of gross tumor volume and radiotherapy dose on prognosis of three dimensional conformal radiation therapy (3D-CRT) for locally advanced non-small cell lung cancer (NSCLC). Methods There were 78 locally advanced NSCLC patients receiving 3D-CRT as study subjects. Three dimensional conformal radiation planning system and CT screening were applied for delineating corresponding target sections, as GTV-T, GTV-P and GTV-N. Gross tumor volume and radiotherapy dose in each target section were analyzed for their prognosis effects. Results Patients with tumor diameter<5.00 cm had higher survival rate than those with tumor diameter≥5.00 cm (P<0.05). Patients with GTV-T<100.00 cm3 had obviously higher survival rate than those with GTV-T≥100.00 cm3 (P<0.05). Stratification analysis showed that in subgroup with radiotherapy dose ≤66 Gy, the survival rate increased while gross tumor volume declined. Conclusion Gross tumor volume shown by three dimensional conformal radiation planning system and CT screening has remarkable influence on long-term survival rate in NSCLC patients. It is also beneficial for locally advanced NSCLC patients receiving large radiotherapy dose for small tumor volume.%目的:探讨肿瘤体积和放疗剂量对局部晚期非小细胞肺癌(NSCLC)三维适形放疗(3D-CRT)预后的影响。方法78例接受3D-CRT的局部晚期NSCLC患者为研究对象,利用三维适形放射计划系统和CT扫描勾画相应靶区,分别定义为GTV-T、GTV-P和GTV-N,分析各靶区肿瘤体积和放疗剂量对3D-CRT的预后效果。结果全组研究对象中肿瘤最大直径<5.00 cm的患者生存率高于肿瘤最大直径≥5.00 cm的患者(P<0.05);GTV-T<100.00 cm3的患者生存率明显高于GTV-T≥100.00 cm3的患者(P<0.05)。分层分析显示放疗处方剂量≤66 Gy亚组中,肿瘤大体体积越小,生存率越高。结论应用三维适形放射计划系统和CT扫描所勾画的大体肿瘤体积对接受

  7. Evaluation of epidermal growth factor receptor tyrosine kinase inhibitor to treat patients with advanced non-small cell lung cancer%表皮生长因子受体酪氨酸激酶抑制剂治疗晚期非小细胞肺癌临床观察

    Institute of Scientific and Technical Information of China (English)

    王光辉; 许阳; 刘勇谋; 张金萍

    2014-01-01

    Objective To investigate the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibi -tor (EGFRT-TKI) in treatment of advanced non-small cell lung cancer (NSCLC).Methods Patients with advanced NSCLCof 160 cases underwent EGFR-TKI gefitinib or erlotinib treatmen,t of which 77 cases (48.1%) as first-line treatment group,83 cases (51.9 %) as second-line treatment group.The clinical features, treatment outcome and survival time were observed ,and evaluated the drug safety.Results The total effective rate of EGFR-TKI was 33.8% (54/160), disease control rate was74.4% (119/160).The median survival time of no progress was 9.8 months, the median survival time was 14.5 months, 1year survival rate was 55%.Multivariate Logistic regression analysis showed,pathological type,skin rash and changes of serumCEA associated with the effective rate ( P <0.05); pathological type, smoking history, skin rash, changes of serum CEAwere correlated with disease control rate ( P <0.05); pathological types were independent factors affecting the progressionfree surviva,l PS was an independent prognostic factors for survival .The first-line and second-line treatment efficacy were similar.Adverse drug reactions including rash and mild diarrhea .Concluis on It demonstrated that the EGFR-TKI is safety andeffective in treatment of advanced NSCLC .%目的:评价表皮生长因子受体酪氨酸激酶抑制剂( EGFRT-TKI)治疗晚期非小细胞肺癌( NSCLC)的疗效及安全性。方法晚期NSCLC患者160例使用EGFR-TKI吉非替尼或厄洛替尼治疗,其中77例(48.1%)为一线治疗组,83例(51.9%)为二线治疗组。观测其临床特征、治疗效果及生存时间,并对药物安全性进行评估。结果EGFR-TKI治疗总有效率为33.8%(54/160),疾病控制率为74.4%(119/160)。无进展中位生存时间为9.8个月,中位生存时间为14.5个月,1年生存率为55%。 Logistic多因素回归分析显

  8. Toxicity Reducing and Efficacy Enhancing Effect of Sodium Cantharidinate Vitamin B6 Injection on GP Chemotherapy Regimen in Treatment of Advanced Non-Small Cell Lung Carcinoma%斑蝥酸钠维生素B6注射液对GP方案治疗晚期非小细胞肺癌减毒增效作用观察

    Institute of Scientific and Technical Information of China (English)

    曹晶杰; 宋一雪; 蒋潮涌

    2013-01-01

    Objective To observe the efficacy and the influence on the immune function and analgesic effect of Sodium Cantharidinate and Vitamin B6 Injection in treating advanced non-small cell lung carcinoma (NSCLC) patients combined with GP chemotherapy. Methods Totally 79 patients with advanced NSCLC were randomly divided into the observation group and the control group. The observation group accepted GP chemotherapy plus Sodium Cantharidinate and Vitamin B6 Injection, and the control group was treated with GP chemotherapy. After 2 cycles of chemotherapy, the efficacy was evaluated, cellular immune function index and analgesic effect were observed. Results The objective response rate (RR) of the treatment group was 72.50%(29/40), and the control group was 48.72%(19/39). There was no significant difference between the two groups (P>0.05). After 2 cycles of treatment, the ratio of CD3+, CD4+, CD8+, CD4+/CD8+ and NK in the observation group were higher than the control group, with significant differences (P<0.05). The pain relief rate in the observation group was 75.00%(30/40), and it was 51.28%(20/39) in the control group, the difference was significant between the two groups (P<0.05). Conclusion Sodium Cantharidinate and Vitamin B6 Injection combined with GP chemotherapy can improve the short-term effect rate and the cellular immune function. It can also relieve the pain and improve the guality of life of patients with advanced NSCLC.%目的观察斑蝥酸钠维生素B6注射液对接受GP方案(吉西他滨+顺铂)治疗的晚期非小细胞肺癌(NSCLC)患者临床疗效、免疫功能及止痛效果的影响。方法将79例晚期NSCLC患者分为观察组和对照组,2组患者均给予GP方案化疗,同时观察组予斑蝥酸钠维生素B6注射液治疗,疗程为2个周期。评价2组近期疗效,对比免疫功能,并评估止痛效果。结果观察组的客观缓解率为72.50%(29/40),对照组为48.72%(19/39),差异有统计学意义(P<0.05)

  9. EGFR-TKI联合化疗治疗EGFR-TKI获得性耐药的晚期非小细胞肺癌疗效分析%Efficacy of EGFR-TKI and chemotherapy in advanced non-small cell lung cancer with EGFR-TKI resistence

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Background and purpose:New treatment strategies should be explored for non-small cell lung cancer (NSCLC) patients after the failure of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). To compare the efficacy and toxicities of chemotherapy in combination with EGFR-TKI or single chemotherapy in advanced NSCLC patients with EGFR-TKI resistence. Methods:In this study, 18 patients were enrolled. Eight patients were treated by chemotherapy combined with EGFR-TKI (CE group);10 patients were treated by single chemotherapy (E group), 21 days for one cycle. All patients received at least 2 cycles of treatment. Results:All 18 patients had been evaluated. The CE group was similar to the E group in objective response rate (ORR:25%vs 10%, P=0.832). The CE group was higher than the E group in disease control rate (DCR:87.5%vs 30%, P=0.046). The median PFS was longer in CE group (3.5 months vs 2.4 months, P=0.05). The CE group was higher than the E group in rash (75%vs 10%, P0.05). Conclusion:Though there was no significant difference in ORR between the 2 groups (P>0.05), the CE group was superior to the E group in DCR and PFS. Patients with retreatment of advanced NSCLC after the failure of EGFR-TKI can be controlled by continued EGFR-TKI and chemotherapy.%  背景与目的:对于(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI)治疗失败的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者亟需探索新的治疗策略来延缓或克服EGFR-TKI的获得性耐药。本研究旨在比较对此类患者采用化疗联合EGFR-TKI与单化疗的疗效及不良反应。方法:符合入组标准的18例患者中,8例接受化疗联合EGFR-TKI(CE组),10例接受单化疗(C组),21 d为1个周期,至少完成2个周期化疗的患者进行疗效及不良反应评价。结果:18例患者均可评价疗效,其中CE组客观反应率(objective response rate,ORR)为25%,C组ORR为10%,两组比

  10. 复方苦参注射液联合GP方案治疗晚期非小细胞肺癌的Meta分析%Meta-analysis on treatment of advanced non-small cell lung cancer with compound matrine injection in combination with Gemcitabine and Cisplatin chemotherapy

    Institute of Scientific and Technical Information of China (English)

    丰育来; 潘守杰; 杨宁娟; 殷长春

    2015-01-01

    目的:系统评价复方苦参注射液联合GP方案治疗晚期非小细胞肺癌的有效性及安全性。方法计算机检索Cochrane Library、PubMed、中国生物医学文献数据库、中国期刊全文数据库、万方数据库、中文科技期刊全文数据库,检索时限为各数据库建库时间至2012年9月,搜索复方苦参注射液联合GP方案化疗对比单纯GP方案治疗晚期非小细胞肺癌的临床随机对照试验,任何语言的文献都在检索范围之内,由2名评价者独立评价并交叉核对纳入研究质量后,采用RevMan 5.2软件进行Meta分析。结果共纳入12篇随机对照试验。 Meta分析结果显示:与单纯GP方案化疗相比,复方苦参注射液联合GP方案治疗晚期非小细胞肺癌能提高近期疗效[OR=1.39,95%CI(1.08,1.79),P=0.01],改善患者的生活质量[OR=3.29,95%CI(2.30,4.71),P<0.00001],减少白细胞下降[RR=0.45,95%CI(0.31,0.65),P<0.0001],减轻呕吐反应[RR=0.38,95%CI(0.26,0.56),P<0.00001]。结论复方苦参注射液联合GP方案治疗晚期非小细胞肺癌能提高近期疗效,改善患者的生活质量,减少严重的化疗毒副反应。但需要更大样本的临床随机对照试验来进一步证实。%Objective It is to systematically evaluate the effectiveness and safety in the treatment of advanced non-small cell lung cancer (NSCLC).Methods Cochrane library, PubMed, CBM, CNKI, VIP, WANFANG DATA and Traditional Chinese Medicine Database System were searched through computers.The search was finished in September 2012.Random-ized controlled trials ( RCTs) of CMI combining Gemcitabine and Cisplatin chemotherapy ( versus chemotherapy alone) in any language were included.Two researchers extracted data and assess literature quality separately, and made meta-analysis by RevMan 5.2 software.Results Totally 12 RCTs were included.The Meta

  11. Clinical research of pemetrexed combination with carboplatin as the therapy in advanced non-small cell lung cancer of senium%培美曲塞联合卡铂治疗老年晚期非小细胞肺癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    赵珺

    2011-01-01

    目的 观察培美曲塞(Pemetrexed,PEM)联合卡铂(carboplatin,CBP)治疗老年晚期非小细胞肺癌(NSCLC)的有效性和毒副反应.方法 49例老年晚期NSCLC患者接受PEM(500 mg/m2)联合CBP(AUC=5)方案化疗.21 d为1个疗程,每例患者至少接受2个疗程.结果 所有患者均可评价疗效,完全缓解(CR)0例,部分缓解(PR)23例,稳定(SD)21例,进展(PD)5例.总有效率(RR)为46.9%(23/49),NSCLC患者ⅢB期有效率68.2%,明显高于Ⅳ期29.6%(x2=3.879,P<0.05),疾病进展时间(TTP)5.3个月,中位生存期(MST)11.2个月(3~21个月),1年生存率为54.3%.毒副反应主要有骨髓抑制、恶心呕吐、腹泻、肝功能受损及粒缺所致发热等.49例中,白细胞减少23例(46.9%)明显高于恶心11例(22.4%)、呕吐5例(10.0%)、肝功能异常4例(8.0%).发热1例(2.0%)(x2=3.879,P<0.05;x2=8.451、8.778、9.123、9.741,均P<0.01).结论 培美曲塞联合卡铂方案可作为老年晚期NSCLC有效的一线化疗方案.%Objective To evaluate the curative effect and toxic reaction of pemetrexed combination with carboplatin as the therapy in advanced non-small cell lung cancer(NSCLC) of senium.Methods A total of 49 chemotherapy naive patients with ⅢB or Ⅳ NSCLC were enrolled in this study.Pemetrexed was given at a dose of 500mg/m2.Carboplatin dosed to an area under the time-concentration curve( AUC ) of 5.The chemotherapy was repeated every 21 days.Each patient was given at least 2 cycles.Results The curative effects of all the patients were evaluated.Among the 49 patients, the symptoms of 23 had been partially response ,21 stabilized and 5 progressed.The total effective rate was 46.9% ( 23/49 ).The efficiency of 68.2% in NSCLC with ⅢB phase were significantly higher than,29.6% in NSCLC with IV phase( X2 = 3.879, P < 0.05 ), Median time to progression (TIP) was 5.3 months.Median survival duration was 11.2 months( 3~ 21 months), and one year survival rate was 54.3%.The major toxicity included neutropenia, nausea

  12. Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Ji-Jie Huang; Shu-Xiang Ma; Xue Hou; Zhao Wang; Yin-Duo Zeng; Tao Qin; Xiao-Xiao Dinglin; Li-Kun Chen

    2015-01-01

    Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinical y characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

  13. 复方苦参注射液联合吉西他滨和顺铂治疗非小细胞肺癌的疗效观察%Efficacy of compound matrine injection in combination with gemcitabine and cisplatin chemotherapy in the treatment of patients with advanced non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘国辉; 李婷

    2012-01-01

    Objective: To observe and compare the efficacy and toxicity of compound matrine injection in combination with CP regimen ( gemcitabine plus cisplatin) and CP regimen in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Methods: One hundred and twenty patients with advanced NSCLC diagnosed by pathology or cytology were assigned to receive either compound matrine injection in combination with CP regimen (matrine group,60 cases) or CP regimen alone (control group,60 cases). After treatment for at least 2 cycles,the curative efficacy was evaluated. Results; The total response rate in matrine group was 40. 00% ; 24 had partial remission, and 24 had stable disease. The total response rate in the control group was 36. 67% ; 22 had partial remission, and 24 had stable disease. The difference of the overall response rate between the two groups was insignificant. The pain remission rate in matrine group (37 patients with cancer pain) was 86.49% and that in the control group (38 patients with cancer pain) was 52.63% .showing significant difference between the two groups (P<0.05).The incidence rates of leucopenia, II ~ IV gastrointestinal reaction,and hepatorenal toxicity in matrine group were significantly less than control group (P<0.05). Conclusion; Compound matrine injection can alleviate the side effects of CP chemotherapy, thus enhance patients'tolerance to chemotherapy.%目的:观察和比较复方苦参注射液联合吉西他滨和顺铂(GP)的方案与单纯GP方案治疗非小细胞肺癌(NSCLC)的疗效及不良反应.方法:将经病理组织学或细胞学确诊为晚期非小细胞肺癌患者120例作为研究对象,按所接受的方案分为复方苦参注射液联合GP方案组(苦参组)60例及单纯GP方案组(对照组)60例.每例患者至少治疗2周期以上进行疗效评价.结果:苦参组60例:部分缓解( PR)24例,稳定(SD)24例,总有效率为40.00%;对照组60例:部分缓解(PR) 22例,稳定(SD) 24

  14. 中国人群应用培美曲塞与多西他赛单药二线治疗晚期非小细胞肺癌的Meta分析%A Meta-analysis on Pemetrexed and docetaxel single drug in treatment of advanced non-small cell lung cancer of China crowd as second line theraPy

    Institute of Scientific and Technical Information of China (English)

    杨罡; 李劲

    2015-01-01

    Objective It is to evaluate the clinical efficacy and safety of the pemetrexed compared with the docetaxel for treating advanced non-small-cell lung cancer( NSCLC)as second line therapy. Methods Such databases as PubMed,Elsevier Science Direct and CNKI were searched to collect the randomized controlled trials( RCTs)about pemetrexed versus docetaxel for the treatment of NSCLC as second therapy. RevMan 5. 0 soft ware was used for Meta-analyses. Results Seven studies invol-ving 803 patients were included. The results of Meta-analyses showed that,in the aspect of efficacy,there was no significant difference between the two groups in the effective rate,the disease control rate,and the one-year survival rate;in the aspect of safety,compared with docetaxel,pemetrexed could reduce the neutropenia and the alopecia,increase rash. There was no sig-nificant difference in hemoglobin,thrombocytopenia,nausea and vomiting,diarrhea and fatigue between two groups. Conclu-sion Pemetrexed has similar efficacy to docetaxel for advanced NSCLC patients,but it has fewer side effects of neutropenia and alopecia.%目的:比较中国人群应用培美曲塞与多西他赛单药二线治疗晚期非小细胞肺癌的疗效和安全性。方法计算机检索 PubMed、Elsevier Science Direct、CNKI等数据库,收集中国人群应用培美曲塞与多西他赛单药二线治疗晚期肺非小细胞肺癌的随机对照试验,用Cochrane协作网提供的Revman 5.0软件对数据进行Meta分析。结果共纳入7个研究,803例患者,Meta分析结果显示:在疗效方面,2组的有效率、疾病控制率、1年生存率等比较差异无统计学意义。在安全性方面,与多西他赛组相比,培美曲塞组重度中性粒细胞计数下降、脱发发生率低,皮疹发生率高;血红蛋白下降、血小板计数下降、恶心、呕吐、腹泻、乏力等发生率2组比较差异无统计学意义。结论多西他赛与培美曲塞单药二线治疗晚期

  15. 晚期非小细胞肺癌患者一线化疗前纤维蛋白原状态与预后的相关性%Correlative Study on Plasma Status of Fibrinogen and Prognosis in Patients with Advanced Non-small Cell Lung Cancer Receiving First-line Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    龚晶; 曲秀娟; 刘云鹏; 滕月娥; 张敬东; 赵明芳; 金波; 于萍; 石晶

    2013-01-01

    目的 探讨晚期非小细胞肺癌一线化疗患者血浆纤维蛋白原状态与预后的相关性.方法 回顾分析不同临床病理特征患者中化疗前纤维蛋白原状态,并进行生存分析.结果 236例患者中纤维蛋白原升高的发生率为56.6%,与病理类型、分期、吸烟史、性别、功能状态(PS)评分及年龄无明显关系.PS评分(HR=1.85,P<0.001)及纤维蛋白原升高(HR=1.63,P=0.008)为总生存的预后不良因素.化疗前纤维蛋白原正常和升高的患者其中位总生存期分别为20.8和15.1个月,两者比较差异有统计学意义(P=0.008);无疾病进展时间分别为8.5和5.5个月,两者比较差异无统计学意义(P=0.132).结论 化疗前血浆纤维蛋白原升高是晚期非小细胞肺癌一线化疗患者的预后不良因素,生存期明显缩短.监测纤维蛋白原状态不仅是预防患者出现血栓等凝血性疾病的有效措施,还可作为非小细胞肺癌发展、预后判断及辅助治疗的实验室指标.%Objective To explore the relationship between plasma fibrinogen status and the prognosis in patients with advanced non-small cell lung cancer who received first-line chemotherapy. Methods We retrospectively analyzed plasma fibrinogen status in different clinical pathological features and the differences of prognosis according to plasma status before chemotherapy. Results The total incidence of hyperfibrinogenemia was 56.6%, and there were no differences in different pathology, stage, history of smoke, sex, age and PS score. Univari-ate analysis revealed that higher levels of fibrinogen (>4 g/L) (HR=1.85,P < 0.001) and PS score (HR=1.63,P =0.008) were negative prognostic factors. The overall survival (OS) in patients with elevated fibrinogen and normal was 15.1 months and 20.8 months at a P-value of 0.008 with significant statistic differences. The progression-free survival (PFS) in different fibrinogen status was 5.5 months and 8.5 months at a P-value of 0.132 with

  16. Clinical observation on treatment with gefitinib in advanced non-small cell lung cancer patients failed to previous chemotherapy%吉非替尼治疗化疗失败的晚期非小细胞肺癌临床观察

    Institute of Scientific and Technical Information of China (English)

    马锐

    2011-01-01

    目的:评价吉非替尼治疗化疗失败的晚期非小细胞肺癌(NSCLC)的疗效及不良反应.方法:对68例化疗失败的经病理或细胞学证实的晚期NSCLC患者给予吉非替尼250mg,qd,口服,至病情进展或出现不可耐受的不良反应.结果:68例患者中,CR 1例,PR 20例,SD 23例,PD 24例.有效率30.88%(21/68),疾病控制率为64.71%(44/68);全组中位疾病进展时间(TTP)为5.2个月,中位生存时间为9.3个月,1年生存率为52.94%(36/68).与药物相关的不良反应主要为Ⅰ、Ⅱ度皮疹和腹泻,皮疹发生率为26.47% (18/68),腹泻发生率为19.12%(13/68),多在用药后1周内出现,症状轻不需特殊处理.1例出现Ⅰ度转氨酶升高.结论:吉非替尼治疗化疗失败的晚期非小细胞肺癌安全有效,不良反应轻微,患者耐受性和依从性良好.%Objective:To evaluate the efficacy and toxicity of gefitinib in treatment of patients with non - small cell lung cancer ( NSCLC )who failed to previous chemotherapy. Methods: Total of 68 failed to previous chemotherapy patients with advanced NSCLC confirmed by pathology or cytology were treated with oral gefitinib 250 mg/d until disease progression, or intolerated toxicity. Results: Of 68 patients, one patient achieved complete remission ,20 patients achieved partial response, 23 achieved stable disease and 24 had progressive disease. Response rate was 30.88%( 21/68 ) disease control rate 64.71%( 44/68 )median time to progression 5.2 months, median overall survival 9.3 months, 1 -year survival rate 52.94%( 36/68 ). Drug - related toxicity was mainly mild ( 1 or 2 grade )skin reactions and diarrhea. skin reactions occurred in 26.47% of patients ( 18/68 ), diarrhea occurred in 19.12%of patients ( 13/68 ), symptoms more appeared in a week after administration, and could relieve without any special treatment, 1 patient happened mild transaminase elevation. Conclusion: Gefitinib is effiectire and safe to advanced NSCLC failed to previous

  17. Therapeutic effect of imatinib on advanced non-small cell lung cancer Shenlingbaizhu granule combined with gefitinib%参苓白术颗粒联合吉非替尼对晚期非小细胞肺癌的治疗作用

    Institute of Scientific and Technical Information of China (English)

    王永海; 邢建群; 寇丽春

    2015-01-01

    Objective Observation of Shenling Baizhu granule combined with gefitinib in advanced non small cell lung can-cer (NSCLC ) treatment effect .Methods Select diagnosed by pathology or cytology of 40 cases of NSCLC patients ,were ran-domly divided into treatment group and control group ,the patients in the treatment group received oral Shenling Baizhu parti-cles ,6 g/3 times/d ,gefitinib 250 mg/d orally;the control group only received gefitinib 250 mg/d orally ;the two groups were treated for 21 d as 1 chemotherapy cycle ,at least 3 cycles of treatment .A comparison of the short-term efficacy ,quality of life ,the two groups of patients with clinical symptoms improvement and the changes of T cell subset .Results No signifi-cance between the two groups of curative effect in the near future ( P>0 .05 );the treatment group after treatment ,KPS score ,quality of life to improve the clinical curative effect of TCM syndrome was significantly higher than that in control group ( P<0 .05 ) .The treatment group CD4 after treatment than before treatment ( P<0 .05 ) increased .Conclusion Large headed Atractylodes granule combined with gefitinib can significantly improve the life quality of patients with advanced NSCLC ,regulate immune function .%目的:观察参苓白术颗粒联合吉非替尼对晚期非小细胞肺癌(NSCLC )的治疗效果。方法选取经病理组织学或细胞学确诊为NSCLC患者40例,随机分为治疗组及对照组。治疗组患者给予参苓白术颗粒口服,6 g/次,3次/d ,吉非替尼250 mg/d口服;对照组仅给予吉非替尼250 mg/d口服。2组均连续治疗21 d为1个化疗周期,至少治疗3个周期,对比2组患者近期疗效、生活质量、中医症状改善及T细胞亚群变化。结果2组近期疗效比较无统计学意义(P>0.05);治疗组治疗后生活质量KPS评分改善,中医证候临床疗效显著高于对照组( P<0.05),治疗组治疗后CD4较治疗前升高( P<0

  18. 三维适形放疗单用或与不同时段热疗联合治疗局部晚期非小细胞肺癌%Thermotherapy combined with 3-D conformal radiotherapy in different time and sequence in the treatment of locally advanced non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘仙明; 郭建平; 孙建刚; 周尔玺; 王晓燕

    2011-01-01

    目的:评价不同时段深部热疗联合三维适形放疗治疗局部晚期非小细胞肺癌(NSCLC)的临床疗效.方法:回顾性分析我院2006年9月~2010年3月采用三维适形放疗单用或与不同时段深部热疗联合治疗局部晚期 NSCLC患者 91例,其中,单纯行放疗组(A组)31例,放疗后即刻行热疗组(B组)37例,热疗后2 h行放疗组(C组)23例.完成治疗后0~2个月通过CT对近期疗效进行评价.结果:3组有效率分别为A组 51.6%,B组 75.7%和C组78.3%.B组与A组,C组与A组的有效率比较,差异有统计学意义(P0.05).结论:热疗联合三维适形放疗比单纯行三维适形放疗在治疗局部晚期NSCLC短期疗效上更具优势,而热疗联合放疗的时间和顺序对短期疗效无明显影响.%Objective: To evaluate the efficacy of thermotherapy combined with 3-D conformal radiotherapy in different time and sequence in the treatment of locally advanced non-small-cell lung cancer (NSCLC).Methods: 91 patients with locally advanced NSCLC were analyzed retrospectively, who were treated with 3-D conformal radiotherapy only or combined with thermotherapy in different time and sequence in our hospital from September 2006 to March 2010.31 patients were treated with 3-D conformal radiotherapy only (group A), 37 patients were treated with thermotherapy after 3-D conformal radiotherapy immediately (group B), 23 patients were treated with 3-D conformal radiotherapy after thermotherapy at an interval of about 2 hours (group C).The short-term effects were evaluated through CT scan after therapy of 0-2 months.Results: The effective rate of group A was 51.6%, and that of group B and group C was 75.7% and 78.3%, the differences between group A and B, group A and C were significant (P<0.05), and there was no significant difference between group B and C (P>0.05).Conclusion: The patients treated with thermotherapy combined with 3-D conformal radiotherapy can obtain better short-term effects than those

  19. XRCC1和XRCC3单核苷酸多态性与晚期非小细胞肺癌铂类药物化疗疗效的相关性%Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    许崇安; 王小杰; 张晔; 李琳

    2011-01-01

    背景与目的 DNA修复基因多态性预测铂类药物化疗敏感性对非小细胞肺癌(non-small cell lung cancer,NSCLC)个体化治疗具有重要意义.本研究旨在探讨X线修复交错互补基因1(X-ray repair cross complementing gene 1,XRCC1)和X线修复交错互补基因3(X-ray repair cross complementing gene 3,XRCC3)单核苷酸多态性与晚期NSCLC患者对铂类药物化疗疗效的关系.方法 采用PCR-RFLP方法检测130例以含铂方案化疗的晚期NSCLC患者外周血DNA中XRCC1 Arg194 Trp、Arg399 Gln和XRCC3 Thr241 Met基因多态性,分析其基因型与化疗疗效的关系.结果 130例晚期NSCLC患者采用含铂方案化疗2个周期后,化疗总有效率为33.8%.XRCC1 194和399基因多态性与铂类药物化疗敏感性相关,而XRCC3 241基因多态性与化疗敏感性无关(P=0.145).携带至少1个XRCC1 194 Trp等位基因者化疗有效率至少是携带Arg/Arg基因型患者的2.5倍(42.1%vs22.2%,OR=2.545,95%CI:1.159-5.590,P=0.020).携带XRCC1399 Arg/Arg基因型者的化疗有效率为45.5%,明显高于携带至少1个Gln等位基因者(21.9%)(OR=0.336,95%CI:0.156-0.722,P=0.005).XRCC1 194和399基因多态性之间存在联合作用,同时携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率明显高于同时携带194 Arg/Arg和399 Arg/Gln基因型者(44.4% vs 18.8%,OR=3.467,95%CI:1.223-9.782,P=0.019).XRCC1和XRCC3基因多态性在化疗敏感性方面存在一定的联合作用,携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg野生型基因同时又携带XRCC3 241 Thr/Met基因型者的化疗有效率明显高于其它基因型携带者.结论 XRCC1和XRCC3的多态联合可能与晚期NSCLC患者对铂类药物化疗疗效具有相关性.%Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung

  20. Nutritional status of patients with advanced non -small cell lung cancer and the effect of nutritional support on chemotherapy%晚期非小细胞肺癌患者的营养状况及营养支持对其化疗的影响

    Institute of Scientific and Technical Information of China (English)

    梁彩霞; 吴家园; 江丹贤; 陈满瑜; 庞雅君; 胡利人

    2015-01-01

    Objective:To investigate the nutritional status of patients with advanced non -small cell lung cancer (NSCLC)and the effect of nutritional support on the efficiency and toxicity of chemotherapy and nutrient indicators. Methods:Totally 60 patients with advanced NSCLC were randomly divided into nutritional support group and control group with TP chemotherapy.NRS -2002 was used to perform nutritional risk screening before chemotherapy.The nu-tritional support group were given the nutritional support during chemotherapy,while the control group was given clini-cal routine treatments.Compared the efficiency and toxicity of chemotherapy and the changes of nutrient indicators. Results:The incidence of nutritional risk of hospitalized patients with advanced NSCLC was 61.7%.Compared with the control group,the effective rate of chemotherapy of the nutritional support group had no significant difference.The incidence of bone marrow suppression was significantly lower in the nutritional support group than that of the control group.There was no significant difference of nutrient indicators such as BMI,ALB,Hb and PA between two groups be-fore chemotherapy.The nutrient indicators of BMI,ALB,Hb and PA in the nutritional support group were improved af-ter chemotherapy,while only ALB was improved in the control group.The nutrient indicators of the nutritional support group were significantly better than the control group after treatment.Conclusion:Patients with advanced NSCLC have a high incidence of nutrition risk.Nutritional support can improve the nutritional status of patients with advanced NSCLC and reduce the toxicity of chemotherapy.%目的:探讨晚期非小细胞肺癌患者的营养状况及营养支持对患者的临床疗效和营养指标的影响。方法:选取我院收治的晚期非小细胞肺癌住院患者60例,随机分为营养支持组和对照组,均采用 TP 方案进行化疗。在化疗前应用 NRS -2002量表进行营养风险评估,在化疗

  1. Changes and significance of serum IL-1 and GH/IGF-1 levels in advanced non-small cell lung cancer patients with cachexia%晚期非小细胞肺癌恶病质患者血清IL-1和GH/IGF-1水平的变化及意义

    Institute of Scientific and Technical Information of China (English)

    何婧; 缪捷飞; 钱俐

    2016-01-01

    目的:观察晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)恶病质患者血清白细胞介素-1(interleukin-1, IL-1)、生长激素(growth hormone, GH)/胰岛素样生长因子-1(insulin-like growth factor 1, IGF-1)水平的变化及其意义。方法:选取41例晚期NSCLC恶病质患者为恶病质组;42例晚期NSCLC非恶病质患者为非恶病质组;另选取24例健康就诊者为对照组。检测所有入选者的营养参数包括体质量指数(body mass index, BMI)、上臂中部臂围(mid-upper arm circumference, MAC)及血清白蛋白(albumin, ALB);并用酶联免疫吸附法检测入选者血清IL-1、GH和IGF-1的含量。结果:(1)与对照组相比,非恶病质组BMI、MAC及ALB的差异无统计学意义(P>0.05),恶病质组BMI、MAC及ALB均明显降低(P<0.05);与非恶病质组相比,恶病质组BMI、MAC及ALB均明显降低(P<0.05)。(2)与对照组相比,非恶病质组及恶病质组血清IL-1、GH及IGH表达均明显增加(P<0.05),恶病质组GH/IGF-1升高(P<0.05);与非恶病质组相比,恶病质组血清IL-1及GH表达增加(P<0.05),而IGF-1表达降低(P<0.05),GH/IGF-1升高(P<0.05)。结论:晚期NSCLC恶病质患者营养状况明显恶化,IL-1和GH/IGF-1的变化可能介导了晚期NSCLC患者恶病质的发生。%Objective:To study the expression of serum interleukin-1(IL-1) and growth hormone/insulin-like growth factor 1 (GH/IGF-1) levels in advanced non-small cell lung cancer(NSCLC) patients with cachexia and its significance. Methods: 41 cases of NSCLC patients with cachexia were used as the cachexia group; 42 cases of NSCLC patients without cachexia were used as the non-cachexia group; and 24 healthy people were taken as normal controls. All the subjects were tested the nutrition index such as:body mass index(BMI), mid-upper arm circumference(MAC) and serum albumin(ALB);and the serum levels of IL-1, GH and IGF-1 were detected by enzyme-linked immunoabsorbent

  2. Survival benefit and failure patterns of EGFR-TKIs in elderly patients with advanced non-small cell lung cancer%EGFR-TKIs治疗老年非小细胞肺癌的生存获益及失败情况分析

    Institute of Scientific and Technical Information of China (English)

    陈华军; 杨衿记; 严红虹; 王震; 汪斌超; 黄逸生; 吴一龙

    2012-01-01

    Objective To investigate the survival benefit and failure patterns of epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs) in elderly patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 71 NSCLC patients with age >65 with acquired resistance to gefitinib or erlotinib in our hospital during June 2002 to August 2011 were enrolled in this study. EGFR gene mutation in tumor tissue was tested by direct sequencing. Survival benefit and failure sites were analyzed. Results Median progression-free survival (mPFS)and median overall survival (mOS)in the cohort were 10.0 months and 18. 0 months respectively. mOSs in patients with EGFR activating mutations, wild-type or unknown status were 18. 0, 21. 6 and 14. 3 months, respectively (P =0. 200). EGFR-TKIs in the first-line setting or other settings could produce comparable mOSs (18.0 vs 17.8 months, P =0.631). Failure included 3 patterns; 26.8% with pre-existing lesions progression, 42.2% with occurrence of new lesions, and 31.0% with both. Failure patterns were not correlated with EGFR mutational status (r = -0. 05, P = 0. 648). Patients of 25. 4% were with extracranial progression, and 8. 5% with intracranial progression. Only cranial failure was found in 11. 1% of patients with baseline brain metastasis. Conclusion EGFR-TKIs produced rational survival benefit in Chinese elderly NSCLC. New lesions tend to occur on treatment failure, and progressive lesions limited in brain are seldom observed.%目的 探讨表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)治疗老年非小细胞肺癌(non-small cell lung cancer,NSCLC)的生存获益及失败情况.方法 回顾性分析71例≥65岁的NSCLC患者,接受吉非替尼或厄洛替尼治疗后出现失败.直接测序法检测肿瘤组织的EGFR基因突变.分析不同亚组的生存获益及病灶进展部位.结果 全组mPFS为10.0个月;mOS为18.0个月,EGFR

  3. DC-CIK联合化疗治疗晚期非小细胞肺癌的临床疗效%Dendritic cell-cytokine induced killer cells combined with chemotherapy in treatment of advanced non-small cell lung cancer patients: The clinical effectiveness

    Institute of Scientific and Technical Information of China (English)

    张俊萍; 王江涛; 贾林梓; 毛光华; 史天良; 杨晓玲; 肖艳; 张丽彬; 冯慧晶; 韩亚萍; 智婷

    2011-01-01

    Objective: To evaluate the safety and therapeutic effect of dentritic cell (DC) -cytokine induced killer cells (CIKs) combined with chemotherapy in treatment of advanced non-small cell lung cancer (NSCLC) patients. Methods; Fifty patients with advanced NSCLC ( stage Ⅲ to Ⅳ ) , who were admitted to Tumor Hospital of Shanxi Province from August 2008 to January 2010, were treated by DC-CIK combined with chemotherapy (docetaxel + cisplatin) and were taken as the combined treatment group; another fifty advanced NSCLC patients who were treated with chemotherapy alone ( docetaxel + cisplatin) during the same period were taken as controls. The immune function, therapeutic effect, 1-year survival , life quality, and side effects were compared between the two groups. Furthermore, the safety and therapeutic effects of DC-CIK therapy were observed. Results; DC-CIK cells from NSCLC patients were successfully induced, the ratios of CD3+ CD8+ and CD3 + CD56+ cells in DC-CIK cells were significantly increased after culture (P <0.05). There were no obvious changes of T cell subsets in the peripheral blood after combined therapy, and the therapy increased IFN-γ level (P < 0.05). In the chemotherapy group, the ratios of CD3+CD4 + , CD3+ CD8+, CD3- CD56 + cells and IL-2, TNF-α levels were significantly decreased after cell culture (P < 0.05); and the ratios of CD3+ CD8+ , CD3+ CD56 + cells in DCCIK was increased ( P < 0.05 ) . The disease control rate ( DCR) of combined therapy group was higher than that in chemotherapy group (78.0% vs 56.0% , P <0.05) ; the 1-year survival rates of combined therapy group and chemotherapy group were 50% and 44% , respectively, showing no significant difference (P>0.05). The combined therapy group had less side effects(including bone marrow suppression, nausea and vomiting, and peripheral nerve toxicity) compared with the control chemotherapy group ( P < 0.05). The physical condition and appetite of NSCLC patients in the combined

  4. Effectiveness and Safety of Recombinant Human Endostatin Combined with Concurrent Chemoradiotherapy for Advanced Non-small Cell Lung Cancer:a Meta-Analysis%重组人血管内皮抑素联合同步放化疗治疗晚期非小细胞肺癌疗效和安全性Meta分析

    Institute of Scientific and Technical Information of China (English)

    徐慧琳; 戈伟; 曹德东; 明平坡; 郑永法; 宋婧; 罗卫

    2014-01-01

    Objective To evaluate the effectiveness and safety of recombinant human endostatin combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy for advanced non small cell lung cancer ( NSCLC) . Methods Electronic databases including the Cochrane library, PubMed, the Chinese biomedical literature database, China national knowledge internet(,EMbase,VIP and Wanfang database system were searched,until August,2013. The inclusion criteria was efficacy and safety studies of randomized controlled clinical studies in which recombinant human endostatin combined with concurrent chemoradiotherapy was compared with concurrent chemoradiotherapy alone for patients with advanced NSCLC. Cochrane handbook 5. 1. 0 was applied in evaluating the quality of included trials and RevMan 5. 1. 0 software was used for data analysis.Results Five studies including 217 cases of advanced NSCLC were included. The results of the meta-analysis exhibited that compared with concurrent chemoradiotherapy alone, recombinant human endostatin combined with concurrent chemoradiotherapy could increase effective rate [OR=2. 62,95%CI(1. 41,4. 86),P=0. 002]. But there were no significant differences in clinical benefit rate [OR=2. 08,95%CI(0. 92,4. 73),P=0. 08],one year survival rate [OR=1. 18,95%CI(0. 53,2. 66),P=0. 68], improvement in quality of life [OR=1. 57,95%CI(0. 40,6. 07),P=0. 52],rate of leucopenia [OR=1. 25,95%CI(0. 72,2. 17), P=0.43],radioactive esophagitis [OR=1. 16,95%CI(0. 42,3. 21),P=0. 77] and radiation pneumonitis [OR=2. 47,95%CI (0. 34,17. 68),P=0. 37]. Conclusion Compared with concurrent chemoradiotherapy alone,recombinant human endostatin combined with concurrent chemoradiotherapy may be more effective for advanced NSCLC,whereas improvement of life quality and toxicities are similar. For the quality restriction and possible publication bias of the included studies,more high quality randomized controlled trials are required to further verify this conclusion.%目的:

  5. 吉非替尼与普通化疗一线治疗晚期非小细胞肺癌的比较研究%A Comparative Study of Gefitinib and Traditional Chemotherapy in First-line Treatment of Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    孙薇薇; 陈文

    2014-01-01

    Objective: Based on published literatures, the study aimed to compare the efficacy, safety and cost-effectiveness of gefitinib with traditional chemotherapy in first-line treatment of EGFR-mutation advanced non-small cell lung cancer (NSCLC). Methods:A systematic review method was performed to search and retrieve the evidence from various databases including Pubmed, Medline, CNKI, etc. We collected English and Chinese studies during last decade on comparison of gefitinib with traditional chemotherapy in first-line treatment of NSCLC. Results:With inclusion and exclusion criteria, there were 5 clinical studies and 2 cost-effectiveness studies finally recruited for the analysis. Clinical results showed that progression-free survival and objective response rate favored gefitinib in the first-line treatment of EGFR-mutation NSCLC. Also gefitinib was proved to be superior to traditional chemotherapy in safety and improvement in quality of life. Two cost effectiveness studies revealed that from the perspective of UK NHS and Singapore society, gefitinib was cost effective compared with traditional chemotherapy. Conclusions:Gefitinib can be considered as a standard option in the first-line treatment of EGFR-mutation NSCLC. More evidences on cost and cost effectiveness of gefitinib for EGFR-mutation NSCLC patients in China are still needed to support clinical usage and local public decision making on health insurance benefits update in China.%目的:通过文献系统综述,对吉非替尼和普通化疗一线治疗EGFR突变阳性的晚期非小细胞肺癌的临床疗效、安全性、生命质量和成本-效果进行比较研究。方法:在Pubmed、Medline、中国期刊全文数据库(CNKI)等检索近10年发表的比较吉非替尼和化疗一线治疗晚期NSCLC的文献。结果:纳入临床研究5个,显示吉非替尼在改善无进展生存期和客观缓解率上好于化疗,安全性和生活质量的改善好于化疗。2个成本-效果研究

  6. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu;

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

  7. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  8. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma%一线含铂两药化疗方案治疗117例老年晚期非小细胞肺癌的疗效分析

    Institute of Scientific and Technical Information of China (English)

    张黎黎; 王莉; 陈卓; 张林; 刘堃

    2013-01-01

    目的 观察以铂类药物为基础联合吉西他滨(GEM)、长春瑞滨(NVB)、紫杉醇(TAX)或其他一线化疗药物两药化疗对术后晚期非小细胞肺癌(NSCLC)老年患者的疗效,并分析影响预后的临床病理因素.方法 117例老年(>60岁)晚期NSCLC患者,术后分别给予GP(GEM+铂类)、NP(NVB+铂类)、TP(TAX+铂类)、其他一线化疗药物+铂类共四种化疗方案,对其资料进行回顾性研究,分析性别、手术方式、病理类型、分化程度、临床分期与患者预后的关系.绘制Kaplan-Meier生存曲线,采用log-rank进行假设检验,采用Cox比例风险回归模型筛选独立预后因素.结果 117例患者的1、3、5年生存率分别为47.23%、17.52%、8.05%.GP、TP、NP组和其他化疗药物组的无进展生存期(PFS)分别为6.0、5.2、6.1和5.5个月(P>0.05),中位PFS为5.7个月.单因素和多因素分析均显示肿瘤分化程度和临床分期是独立的预后因素.结论 一线含铂两药化疗方案治疗老年晚期NSCLC的疗效与肿瘤分化程度及临床分期有关,但GP、NP、TP及其他一线化疗药物+铂类的疗效无显著差异.%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,pathological types,differentiation,clinical stages).The survival curve was plotted with Kaplan

  9. 培美曲塞与多西紫杉醇二线治疗晚期非小细胞肺癌的Meta分析%Compare pemetrexed with docetaxel in second-line treatment of patients with advanced non-small cell lung cancer:a systematic review

    Institute of Scientific and Technical Information of China (English)

    秦虹; 张晓丽; 阮志华

    2014-01-01

    目的:通过系统评价的方法比较培美曲塞单药和多西紫杉醇单药二线治疗晚期非小细胞肺癌(NSCLC)的疗效与安全性。方法通过Cochrane系统评价的方法,收集文献进行评价与筛选,数据提取,采用 RevMan5.0进行数据分析。结果共纳入9篇研究,1439例患者。Meta分析结果提示:晚期 NSCLC的二线治疗中,培美曲塞与多西紫杉醇相比,治疗有效率(RR=1.26,95%CI:0.93~1.71,P=0.14),疾病控制率(RR=0.97,95%CI:0.88~1.06,P=0.49)及1年生存率(RR=0.98,95%CI:0.81~1.19,P=0.87)差异均无统计学意义;对于Ⅲ~Ⅳ级中性粒细胞减少(RR=0.17,95%CI:0.12~0.23,P<0.01),血小板减少(RR=7.01,95%CI:1.87~26.29,P=0.004)],中性粒细胞性发热(RR=0.19,95%CI:0.07~0.52,P<0.01),脱发(RR=0.09,95%CI:0.01~0.7,P=0.02)及腹泻(RR=0.12,95%CI:0.02~0.65,P=0.01)不良反应,培美曲塞较多西紫杉醇轻。其他不良反应差异无统计学意义(P>0.05)。结论培美曲塞与多西紫杉醇在晚期 NSCLC二线治疗中疗效相当,但培美曲塞的安全性更好。%Objective Evaluating the efficacy and safety of pemetrexed alone versus docetaxel alone in second-line treatment of patients with advanced non-small cell lung cancer(NSCLC).Methods Followed by literature collection,assessment,data collection and extraction according Cochrane handbook for systematic reviews,and data analysis were performed by RevMan 5 .0 software.Re-sults 9 studies involving 1 439 cases were included.The results of Meta-analysis showed that for second-line treatment of advanced NSCLC,in efficacy part,there was no statistical difference between the two group in the effective rate(RR=1.26,95%CI:0.93-1.71,P=0.14),the disease control rate(RR=0.97,95%CI:0.88-1.06,P=0

  10. 吉非替尼记名供药计划治疗晚期复发非小细胞肺癌的疗效和预后因素分析%Analysis of the efficacy and safety of gefitinib in the treatment of recurrent advanced non-small cell lung cancer in an expanded access program (EAP)

    Institute of Scientific and Technical Information of China (English)

    黄河; 张阳; 赵洪云; 王志强; 徐菲; 徐光川; 张力; 管忠震

    2009-01-01

    Objective The aim of this study is to evaluate the efficacy and safety of Gefitinib in the treatment of Chinese patients with recurrent advanced non-small-cell lung cancer (NSCLC). Methods 120 patients were enrolled in this trial from September 2002 to March 2005, and 103 patients were evaluable. All patients were histologically or/and cytologically confirmed to have a locally advanced or metastatic NSCLC, and failed to previous standard treatments. The patients received orally 250 mg of Gefitinib once daily until the disease progression or intolerance to toxicity. First evaluation of response was undertaken one month after drug initiation, then every 2 or 3 months till disease progression. Each patient was followed up every 6 months untill death or end of follow-up. Results Among the 103 evaluable patients, the objective response rate was 18.4% (19/103), and the disease control rate was 51.5% (53/103). The median time to progression (mTTP) was 3 months (range: 0.2~40), the median survival time (MST) was 9.8 months (range: 0.5~51), the 1-, 2-, 3-year survival rates were 44.7%, 26.4% and 13.2%, respectively. The TIP of 41 patients was longer than 6 months with a MST of 25.5 months. The results of COX model analysis suggested that the patients with adenocarcinoma, rash and favourable performance status (PS) had longer TIP. The patients with favourable PS and well controlled disease had longer survival time. Adverse events included skin rash, dry skin, diarrhea and elevation of serum glutamate pyruvate transaminase (SGPT), and were usually mild. Conclusion Gefitinib is effective in treatment of patient with recurrent advanced NSCLC. The patients with controlled disease may achieve a long survival, and the adverse reactions are mild and tolerable.%目的 研究吉非替尼治疗中国晚期非小细胞肺癌(NSCLC)患者的安全性和疗效.方法 2002年9月至2005年3月共入选晚期复发NSCLC患者120例,其中可评价疗效者103例.

  11. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  12. Regime of nedaplatin combined with docetaxel in the first-line treatment of recurrent or advanced non-small cell lung cancer%奈达铂联合多西紫杉醇一线治疗复发晚期非小细胞肺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    王建化; 张武; 陈文俊; 原少斐

    2012-01-01

    目的:观察奈达铂联合多西紫杉醇一线治疗复发/晚期非小细胞肺癌( NSCLC)的疗效及急性不良反应.方法:收治既往未行化疗(辅助或新辅助化疗除外)及分子靶向治疗的复发或晚期NSCLC患者85例,随机分为两组,全组可评估疗效的73例:研究组(奈达铂联合多西紫杉醇)36例,对照组(顺铂联合多西紫杉醇)37例.比较两组的近期有效率、中位无进展生存期(PFS)及急性不良反应.结果:研究组和对照组有效率分别为44.4%(16/36)和45.9%(17/37),P=0.098;PFS分别为5.2和5.1个月,P=0.655;Ⅲ+Ⅳ度消化系统急性毒性,恶心及呕吐分别为2.8%(1/36)和27.0%(10/37),P=0.004;食欲下降分别为5.6%(2/36)和32.4%(12/37),P=0.022;肾毒性分别为0(0/36)和5.4%(2/37),P=0.027;血小板下降为11.1%(4/36)和2.7%(1/37),P=0.011.>4个周期为72.2%(26/36)和45.9%(17/37),P=0.032.结论:奈达铂联合多西紫杉醇一线治疗NSCLC,疗效与标准方案相当,但患者对该方案治疗的