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Sample records for advanced nonsmall cell

  1. Radio(chemotherapy in locally advanced nonsmall cell lung cancer

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    Markus Glatzer

    2016-03-01

    Full Text Available Definitive radiochemotherapy is the standard treatment for many patients with locally advanced nonsmall cell lung cancer (NSCLC. Treatment outcomes have improved over the last decades. Several treatment regimens have been shown effective and safe. This review summarises the results of significant studies between 1996 and 2015 on concomitant and sequential radiochemotherapy regimens and radiation dose per fraction. Beside therapy regimens, optimised radiotherapy planning is indispensable to improve outcome and minimise radiation-induced toxicity. An insight into the rationale of radiotherapy planning for stage III NSCLC is also provided.

  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. 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.

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

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    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.

  5. 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

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

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    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.

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

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    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.

  8. 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...

  9. Crizotinib for Advanced Non-Small Cell Lung Cancer

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

  10. Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives

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    Vilmar, A C; Sorensen, J B

    2011-01-01

    of life. We conducted a literature search of tailored treatment already implemented in advanced NSCLC in order to highlight the information required to decide on the optimal oncological treatment for individual patients. 16 studies were identified by literature review. Significantly improved outcome......Treating patients with advanced nonsmall cell lung cancer (NSCLC) is a daunting task but during recent years new options have emerged. By tailoring treatment using either information on histological subtypes of NSCLC or biomarkers it is now possible to improve outcome and maintain stable quality......, respectively. In conclusion, tailoring treatment according to either histological subtype or EGFR mutation status in advanced NSCLC should today be part of daily practice based on current evidence. Future biomarkers need optimisation of methodology and prospective validation before clinical implementation....

  11. Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives

    DEFF Research Database (Denmark)

    Vilmar, A C; Sorensen, J B

    2011-01-01

    Treating patients with advanced nonsmall cell lung cancer (NSCLC) is a daunting task but during recent years new options have emerged. By tailoring treatment using either information on histological subtypes of NSCLC or biomarkers it is now possible to improve outcome and maintain stable quality...... of life. We conducted a literature search of tailored treatment already implemented in advanced NSCLC in order to highlight the information required to decide on the optimal oncological treatment for individual patients. 16 studies were identified by literature review. Significantly improved outcome......, respectively. In conclusion, tailoring treatment according to either histological subtype or EGFR mutation status in advanced NSCLC should today be part of daily practice based on current evidence. Future biomarkers need optimisation of methodology and prospective validation before clinical implementation....

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

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    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.

  13. 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.

  14. 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.

  15. 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.

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

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    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. 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

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

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    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.

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

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    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

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

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    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.

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

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    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.

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

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    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...

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

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    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.

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

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    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.

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

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    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.

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

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    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...

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

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    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

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

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    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.

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

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

    1989-10-01

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

  10. 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.

  11. 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.

  12. 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.

  13. [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.

  14. 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.

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

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    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.

  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. 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.

  18. 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

  19. 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

  20. [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.

  1. Treatment Advances in Locally Advanced and Metastatic Non-Small Cell Lung Cancer

    NARCIS (Netherlands)

    V.M.F. Surmont (Veerle)

    2010-01-01

    textabstractLung cancer is the leading cause of cancer mortality in the United States and Europe. Approximately 85% of the patients with lung cancer have non–small cell lung cancer (NSCLC), which can be classified into squamous, adeno, large cell and not otherwise specified (NOS) histologies. The mo

  2. 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.

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

    Science.gov (United States)

    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.

  4. 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

  5. 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.

  6. 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 ...

  7. 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.

  8. 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.

  9. 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.

  10. Randomized phase II clinical trial of chemo-immunotherapy in advanced nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Eduardo Lasalvia-Prisco

    2008-09-01

    Full Text Available Eduardo Lasalvia-Prisco1,4, Emilio Garcia-Giralt2, Jesús Vázquez2,4, Marta Aghazarian4, Eduardo Lasalvia-Galante3,4, Joshemaria Larrañaga3,4, Gonzalo Spera31Interdoctors Medical Procedures, North Miami Beach, FL, USA; 2Centre De Cancérologie Hartmann, Neuilly Sur Seine, France; 3Interdoctors Medical Procedures, Montevideo, Uruguay; 4National Institute of Oncology, Montevideo, Uruguay (initial dataAbstract: The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate, duration, median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a phytohemaglutinin-induced lymphocyte proliferation, b prevalence of T-Regulatory (CD4+CD25+ cells and for specific immunity: a lymphocyte proliferation induced by tumor-associated antigens (TAA contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy in response rate induced by the two treatments (39.0% and 35.0% was not statistically significant. However, the response duration (22 and 31 weeks, the median survival time (32

  11. 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...

  12. 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.

  13. 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.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe

    Directory of Open Access Journals (Sweden)

    Walleser S

    2012-09-01

    Full Text Available Silke Walleser,1 Joshua Ray,2 Helge Bischoff,3 Alain Vergnenègre,4 Hubertus Rosery,5 Christos Chouaid,6 David Heigener,7 Javier de Castro Carpeño,8 Marcello Tiseo,9 Stefan Walzer21Health Economic Consultancy, Renens, Switzerland; 2F Hoffmann-La Roche Pharmaceuticals AG, Basel, Switzerland; 3Thoracic Hospital of Heidelberg, Heidelberg, Germany; 4Limoges University Hospital, Limoges, France; 5Assessment-in-Medicine GmbH, Loerrach, Germany; 6Hospital Saint Antoine, Paris, France; 7Hospital Grosshansdorf, Grosshansdorf, Germany; 8University Hospital La Paz, Madrid, Spain; 9University Hospital of Parma, Parma, ItalyBackground: First-line maintenance erlotinib in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC has demonstrated significant overall survival and progression-free survival benefits compared with best supportive care plus placebo, irrespective of epidermal growth factor receptor (EGFR status (SATURN trial. The cost-effectiveness of first-line maintenance erlotinib in the overall SATURN population has been assessed and published recently, but analyses according to EGFR mutation status have not been performed yet, which was the rationale for assessing the cost-effectiveness of first-line maintenance erlotinib specifically in EGFR wild-type metastatic NSCLC.Methods: The incremental cost per life-year gained of first-line maintenance erlotinib compared with best supportive care in patients with EGFR wild-type stable metastatic NSCLC was assessed for five European countries (the United Kingdom, Germany, France, Spain, and Italy with an area-under-the-curve model consisting of three health states (progression-free survival, progressive disease, death. Log-logistic survival functions were fitted to Phase III patient-level data (SATURN to model progression-free survival and overall survival. The first-line maintenance erlotinib therapy cost (modeled for time to treatment cessation, medication cost in later lines, and

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

  16. 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....

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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...

  3. 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.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    Chouaïd C

    2014-12-01

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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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...

  12. 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.

  13. 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

  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. 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.

  17. 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.

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Xiao ZHAO

    2012-01-01

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

  2. 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.

  3. 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.

  4. 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

  5. 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...

  6. 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 ...

  7. 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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    Ming Li

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

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

    Science.gov (United States)

    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.

  10. 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.

  11. 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

  12. 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:

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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.

  16. Advances in the management of acquired resistance to EGFR-TKI in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Fei Zhou; Caicun Zhou

    2015-01-01

    Drugs that specifical y target the tyrosine kinase domain of epidermal growth factor receptor (EGFR), such as erlotinib or gefitinib, have exhibited striking ef icacy in non-smal cel lung cancer (NSCLC) patients har-boring activating EGFR mutations. However, acquired resistance inevitably develops and remains a serious barrier for the successful management of patients with this disease. Multiple mechanisms are reportedly involved in the process of acquired resistance, which provide new insights into the management of EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance. Here, we provide an overview of the emerging treatment approaches for patients with EGFR-TKI resistance.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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

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

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    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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

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    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.

  5. BIM Gene Polymorphism Lowers the Efficacy of EGFR-TKIs in Advanced Nonsmall Cell Lung Cancer With Sensitive EGFR Mutations: A Systematic Review and Meta-Analysis.

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    Huang, Wu Feng; Liu, Ai Hua; Zhao, Hai Jin; Dong, Hang Ming; Liu, Lai Yu; Cai, Shao Xi

    2015-08-01

    The strong association between bcl-2-like 11 (BIM) triggered apoptosis and the presence of epidermal growth factor receptor (EGFR) mutations has been proven in nonsmall cell lung cancer (NSCLC). However, the relationship between EGFR-tyrosine kinase inhibitor's (TKI's) efficacy and BIM polymorphism in NSCLC EGFR is still unclear.Electronic databases were searched for eligible literatures. Data on objective response rates (ORRs), disease control rates (DCRs), and progression-free survival (PFS) stratified by BIM polymorphism status were extracted and synthesized based on random-effect model. Subgroup and sensitivity analyses were conducted.A total of 6 studies that involved a total of 773 EGFR mutant advanced NSCLC patients after EGFR-TKI treatment were included. In overall, non-BIM polymorphism patients were associated with significant prolonged PFS (hazard ratio 0.63, 0.47-0.83, P = 0.001) compared to patients with BIM polymorphism. However, only marginal improvements without statistical significance in ORR (odds ratio [OR] 1.71, 0.91-3.24, P = 0.097) and DCR (OR 1.56, 0.85-2.89, P = 0.153) were observed. Subgroup analyses showed that the benefits of PFS in non-BIM polymorphism group were predominantly presented in pooled results of studies involving chemotherapy-naive and the others, and retrospective studies. Additionally, we failed to observe any significant benefit from patients without BIM polymorphism in every subgroup for ORR and DCR.For advanced NSCLC EGFR mutant patients, non-BIM polymorphism ones are associated with longer PFS than those with BIM polymorphism after EGFR-TKIs treatment. BIM polymorphism status should be considered an essential factor in studies regarding EGFR-targeted agents toward EGFR mutant patients.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

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

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    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

  11. 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

  12. {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.)

  13. 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

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

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    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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

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

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    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.

  20. 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.

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

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    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.

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

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    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.

  3. 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

  4. 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

  5. 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.

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

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    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.

  7. 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

  8. 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

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    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

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

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    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

  12. A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer

    Science.gov (United States)

    Wang, Cuihua; Yu, Xuetao; Wang, Wei

    2016-01-01

    Abstract Background: Nonsmall cell lung cancer (NSCLC)-patients treated with standard chemotherapy experienced progression rapidly. A novel therapy based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors showed an increasing potential in several malignancies including advanced NSCLC. Objectives: This article is a meta-analysis aiming to systematically evaluate the efficacy and safety profiles of PD-1/PD-L1 agents in patients with NSCLC. Data sources: Data were collected from eligible studies searched from PubMed, ScienceDirect, and Web of Science. Synthesis methods: Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1/PD-L1 inhibitors versus docetaxel, pooled odds ratio (OR) was calculated for objective response rate (ORR). The overall frequency was estimated for 1-year OS, 1-year progression-free survival, and ORR. A subgroup analysis among NSCLC patients tested with different epidermal growth factor receptor (EGFR) status was also performed to figure out the relationship between EGFR status and efficacy of PD-1/PD-L1 therapies. OR for occurrence of any grade and grade 3 to 5 treatment-related adverse effect was calculated for evaluating the safety of PD-1/PD-L1 therapies. Results: Nine studies were included in this analysis. The pooled HRs for OS and PFS were 0.68 (95% confidence interval [CI] 0.61–0.75) and 0.83 (95% CI 0.75–0.91), respectively, the pooled OR for ORR was 1.83 (95% CI 1.41–2.36), indicating a significant improvement in OS, PFS, and ORR. In the results of subgroup analysis, the HR for OS in NSCLC patients was 1.05 (95% CI 0.69–1.59) in patients with mutant EGFR and 0.66 (95% CI 0.57–0.77) in patients with wild-type EGFR status. OR for occurrence was 0.36 (95% CI 0.28–0.46) in any grade treatment-related adverse effect and 0.18 (95% CI 0.14–0.22) in grade 3 to 5 treatment-related adverse effect, suggesting a superior safety profile of

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  14. 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.

  15. 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

  16. 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.

  17. 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

  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. 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.

  20. [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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  3. 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.

  4. 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.

  5. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-01-23

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  6. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    Science.gov (United States)

    2016-10-13

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent 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; Stage IV Non-small Cell Lung Cancer

  7. 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

  8. 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

  9. 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,

  10. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin......-layed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac® vaccine treatment in patients with progressive NSCLC....

  12. 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).

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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。

  19. 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

  20. 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)

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Characterization of DDR2 Inhibitors for the Treatment of DDR2 Mutated Nonsmall Cell Lung Cancer

    OpenAIRE

    Terai, Hideki; Tan, Li; Beauchamp, Ellen M; Hatcher, John M.; Liu, Qingsong; Meyerson, Matthew; Gray, Nathanael S.; Hammerman, Peter S.

    2015-01-01

    Despite advances in precision medicine approaches over the past decade, the majority of nonsmall cell lung cancers (NSCLCs) are refractory to treatment with targeted small molecule inhibitors. Previous work has identified mutations in the Discoidin Domain Receptor 2 (DDR2) kinase as potential therapeutic targets in NSCLCs. While DDR2 is potently targeted by several multitargeted kinase inhibitors, most notably dasatinib, toxicity has limited the clinical application of anti-DDR2 therapy. Here...

  8. 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.

  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. 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.

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

    Science.gov (United States)

    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.

  12. 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

  13. 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

  14. 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.

  15. 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。

  16. 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

  17. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-06-17

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  18. 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.

  19. 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.

  20. 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

  1. 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 .

  2. 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.

  3. Mutation of the BRAF Genes in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhimin HUANG

    2012-03-01

    Full Text Available BRAF mutations have been found to be a driver mutation and maybe a therapy target in patients with non-small cell lung cancer. This article reviews the current understanding of BRAF gene, its structure, expression, the signal pathway, as well as its relationship with cancer especially the targeted therapies for non-small cell lung cancer.

  4. Urokinase receptor forms in serum from non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Almasi, Charlotte Elberling; Christensen, Ib Jarle; Høyer-Hansen, Gunilla;

    2011-01-01

    To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients.......To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients....

  5. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2016-09-07

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous 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

  6. 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...

  7. 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.

  8. 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

  9. 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.

  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. 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

  13. 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.

  14. 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

  15. 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

  16. 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).

  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. 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.

  19. 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

  20. [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。

  1. [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。

  2. 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.

  3. The Role of Proteasome Inhibition in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mauricio Escobar

    2011-01-01

    Full Text Available Lung cancer therapy with current available chemotherapeutic agents is mainly palliative. For these and other reasons there is now a great interest to find targeted therapies that can be effective not only palliating lung cancer or decreasing treatment-related toxicity, but also giving hope to cure these patients. It is already well known that the ubiquitin-proteasome system like other cellular pathways is critical for the proliferation and survival of cancer cells; thus, proteosome inhibition has become a very attractive anticancer therapy. There are several phase I and phase II clinical trials now in non-small cell lung cancer and small cell lung cancer using this potential target. Most of the trials use bortezomib in combination with chemotherapeutic agents. This paper tends to make a state-of-the-art review based on the available literature regarding the use of bortezomib as a single agent or in combination with chemotherapy in patients with lung cancer.

  4. 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。

  5. 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

  6. 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

  7. THE MANAGEMENT OF BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Scott eOwen

    2014-09-01

    Full Text Available Brain metastases (BM are a common and lethal complication of non-small cell lung cancer (NSCLC which portend a poor prognosis. In addition, their management implies several challenges including preservation of neurological and neuro-cognitive function during surgery or radiation -therapy, minimizing iatrogenic complications of supportive medications, and optimizing drug delivery across the blood brain barrier (BBB. Despite these challenges, advancements in combined modality approaches can deliver hope of improved overall survival and quality of life for a subset of NSCLC patients with BM. Moreover, new drugs harnessing our greater understanding of tumour biology promise to build on this hope. In this mini-review, we revised the management of BM in NSCLC including advancements in neurosurgery, radiation therapy, as well as systemic and supportive therapy.

  8. Diagnosis and Treatment of Leptomeningeal Metastasis in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan XU

    2015-10-01

    Full Text Available Leptomeningeal metastasis (LM is one of the disastrous events in managing advanced non-small cell lung cancer (NSCLC due to severe clinical symptoms and a grave prognosis. Although intrathecal (IT chemotherapy show some effects for LM in advanced NSCLC, the prognosis is still poor (12 wk-14 wk. A large majority (84%-97% of the patients were found to have adenocarcinoma histology. Epidermal growth factor receptor (EGFR senstive mutations were detected in 43.0%-70.5% adenocarcinoma patients with LM. EGFR tyrosine kinase inhibitors (TKIs showed to be effective for LM in selected NSCLC patients in some reseaches, and confer a survival benefit. Furthermore, future trials need be done to determine the effect of EGFR-TKIs treatment in NSCLC-LM patients.

  9. Resistance mechanisms after tyrosine kinase inhibitors afatinib and crizotinib in non-small cell lung cancer, a review of the literature

    NARCIS (Netherlands)

    van der Wekken, Anthonie; Saber, Ali; Hiltermann, Thijo; Kok, Klaas; van den Berg, Anke; Groen, H. J. M.

    2016-01-01

    Targeted treatment of advanced non-small cell lung cancer patients with afatinib in EGFR mutations or crizotinib in ALK translocation results in profound responses but at the same time induces resistance. As both afatinib and crizotinib have only recently been approved for treatment, this review is

  10. Monitoring Response to Antiangiogenic Therapy in Non-Small Cell Lung Cancer Using Imaging Markers Derived from PET and Dynamic Contrast-Enhanced MRI

    NARCIS (Netherlands)

    de Langen, Adrianus J.; van den Boogaart, Vivian; Lubberink, Mark; Backes, Walter H.; Marcus, Johannes T.; van Tinteren, Harm; Pruim, Jan; Brans, Boudewijn; Leffers, Pieter; Dingemans, Anne-Marie C.; Smit, Egbert F.; Groen, Harry J. M.; Hoekstra, Otto S.

    2011-01-01

    With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non-small cell

  11. Prophylactic G-CSF and antibiotics enable a significant dose-escalation of triplet-chemotherapy in non-small cell lung cancer.

    NARCIS (Netherlands)

    Timmer-Bonte, J.N.H.; Punt, C.J.A.; Heijden, H.F.M. van der; Die, C.E. van; Bussink, J.; Beijnen, J.H.; Huitema, A.D.; Tjan-Heijnen, V.C.

    2008-01-01

    In advanced non-small cell lung cancer (NSCLC) the clinical benefit of a platinum-based doublet is only modest, therefore, attenuated dosed three-drug combinations are investigated. We hypothesized that with adequate support a full dosed chemotherapy triplet is feasible. The study was designed as a

  12. 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

  13. TELOMERASE ACTIVITY OF FIBROBRONCHOSCOPIC BRUSHING CELLS IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    吴晓红; 应可净; 张行

    2003-01-01

    Objective: To evaluate the clinical significance of telomerase activity particularly in terms of prognostic impact in non-small cell lung cancer (NSCLC). Methods: The exfoliated cells from fibrobronchoscopic brushing were studied using polymerase chain reaction based on a telomerase repeat amplification protocal assay. Samples were taken from 60 NSCLC and 20 pulmonary infection cases. Results: Telomerase activity was detected in 53 of 60(88.3%) NSCLC specimens from the lesion side and in 5 of 25(20.0%) from the contralateral side but only in 2 of 20 pulmonary infection samples (P<0.05). The telomerase activity levels in NSCLC (medium 0.109) were significantly higher than those in pulmonary infection (medium 0.018, U=4.95, P<0.05). The telomerase activity levels in tumor staged IIIb-IV (medium 0.173) were higher than those in staged I-IIIa (medium 0.132, U=1.899, P<0.05). Conclusion: Telomerase activity is one of the most important marker in patients with NSCLC. Telomerase activity increases with the advance of tumor stage and can be used as a prognostic indicator of advanced NSCLC.

  14. Overview of KRAS-Driven Genetically Engineered Mouse Models of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Sheridan, Clare; Downward, Julian

    2015-01-01

    KRAS, the most frequently mutated oncogene in non-small cell lung cancer, has been utilized extensively to model human lung adenocarcinomas. The results from such studies have enhanced considerably an understanding of the relationship between KRAS and the development of lung cancer. Detailed in this overview are the features of various KRAS-driven genetically engineered mouse models (GEMMs) of non-small cell lung cancer, their utilization, and the potential of these models for the study of lung cancer biology.

  15. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  16. Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Meng Hang

    2015-06-01

    Full Text Available The present study was done to determine whether kaempferol, a natural polyphenol of the flavonoid family, affects Epithelial-Mesenchymal Transition (EMT in non-small cell lung cancer cells. Kaempferol not only inhibited cancer cell proliferation and migration in a dose-dependent manner but also modulated the expression of EMT-related proteins E-cadherin and vimentin which are indispensible to cellular motility, invasiveness and metastasis. These results indicate that kaempferol suppresses non-small cell lung cancer migration by modulating the expression of EMT proteins. Therefore, kaempferol may be useful as a potential anticancer agent for non-small cell lung cancer.

  17. 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

  18. 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.

  19. Targeted therapies and radiation therapy in non-small cell lung cancer; Therapies ciblees et radiotherapie dans les cancers bronchiques non a petites cellules

    Energy Technology Data Exchange (ETDEWEB)

    Rivera, S.; Quero, L.; Wong Hee Kam, S.; Maylin, C.; Hennequin, C. [Service de cancerologie radiotherapie, hopital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris (France); Deutsch, E. [UMR 1030 ' radiosensibilite des tumeurs et tissus sains ' , Inserm, 114, rue edouard-Vaillant, 94805 Villejuif (France); Departement de radiotherapie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France)

    2011-10-15

    Lung cancer is the leading cause of cancer-related death. Between 80-85% of lung cancers are non-small cell lung carcinomas. One third of the patients are diagnosed with locally advanced stage. In this condition, concomitant radio-chemotherapy is the standard treatment for patients with good performance status. Despite important improvements in the last years, non-small cell lung carcinoma prognosis remains poor, with high rates of both local recurrences and metastases. The heterogeneity of molecular characteristics of non-small cell lung carcinoma cells and a better knowledge of potential targets offer promising developments for new pharmacologic agents. Hereafter we will review the currently most studied pathways and the most promising ones for the treatment of locally advanced unresectable non-small cell lung carcinoma. Two of the most attractive pathways where new agents have been developed and assessed in combination with thoracic radiotherapy or radio-chemotherapy are the EGFR pathway (either with the use of monoclonal antibodies or tyrosine kinase inhibitors) and the angiogenesis inhibition. The development of targeted agents could lead to individualized therapeutic combinations taking into account the intrinsic characteristics of tumor cells. Pharmacological modulation of tumour cells radiosensitivity by targeted therapies is only starting, but yet offers promising perspectives. (authors)

  20. Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chun Yin

    2015-02-01

    Full Text Available Background/Aims: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. Methods: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. Results: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. Conclusions: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

  1. 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

  2. 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.

  3. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop

    DEFF Research Database (Denmark)

    Pirker, Robert; Herth, Felix J F; Kerr, Keith M;

    2010-01-01

    Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with advanced non-small cell lung cancer (NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR...... tyrosine kinase inhibitors (EGFR-TKIs). The EGFR-TKI gefitinib has been approved in Europe for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of the EGFR TK. Because EGFR mutation testing is not yet well established across Europe, biomarker......-directed therapy only slowly emerges for the subset of NSCLC patients most likely to benefit: those with EGFR mutations....

  4. 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。

  5. Safety and Efficacy of Vinorelbine in the Treatment of Non-Small Cell Lung Cancer

    Science.gov (United States)

    Faller, Bryan A.; Pandit, Trailokya N.

    2011-01-01

    Lung cancer remains the most frequently diagnosed cancer in the United States, excluding non-melanoma skin cancer. Non-small cell lung cancer (NSCLC) constitutes the majority (more than 80%) of lung cancer diagnoses. Systemic therapy, with either cytotoxic chemotherapy and/or targeted therapies, has been established to provide benefit to patients with NSCLC in both the adjuvant and advanced disease settings. Vinorelbine, a semi-synthetic vinca-alkaloid has been extensively tested alone and in combination with other cytotoxic or targeted agents in the treatment of NSCLC. Its safety has been well established with neutropenia, anemia, nausea, and vomiting being the most frequently encountered toxicities. The data defining the risks and benefits of vinorelbine in the treatment of NSCLC will be summarized. PMID:21695100

  6. TP53 Mutations in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akira Mogi

    2011-01-01

    Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

  7. Novel EGFR Inhibitors in Non-small Cell Lung Cancer: Current Status of Afatinib.

    Science.gov (United States)

    Liao, Bin-Chi; Lin, Chia-Chi; Yang, James Chih-Hsin

    2017-01-01

    Afatinib, a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been approved worldwide as a first-line treatment for advanced non-small cell lung cancer (NSCLC) that harbors activating EGFR mutations. Here, we have reviewed the recent clinical developments in the treatment of lung cancer using afatinib. Emerging data have revealed the overall survival benefit of first-line afatinib therapy in patients with advanced EGFR (del19)-positive NSCLC. Phase III studies of afatinib have shown the effectiveness of afatinib as a second-line treatment for advanced lung squamous cell carcinoma, as well as the benefit of continuing afatinib therapy in combination with cytotoxic chemotherapy for advanced NSCLC after the occurrence of disease progression in patients who are receiving afatinib monotherapy. Therapeutic benefits of afatinib have also been reported in studies of patients with central nervous system metastasis and patients with HER2 mutation. The utility of afatinib-based combination therapies is being investigated in ongoing research.

  8. 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.

  9. 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

  10. Bilateral Choroidal Metastasis from Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Tariq Namad

    2014-01-01

    Full Text Available Breast and lung cancers are the most common primary neoplasms to manifest with choroidal metastases. The incidence of choroidal metastases from metastatic lung cancer was reported to be 2–6.7%. We report a case of bilateral choroidal metastasis from non-small cell lung cancer. A 59-year-old Caucasian female patient, never a smoker, was diagnosed with stage IV lung adenocarcinoma metastatic to the pleura, bones, and the brain. Her initial scan of the chest showed innumerable soft tissue nodules and mediastinal adenopathy compatible with metastatic disease. Her initial brain MRI showed numerous small enhancing lesions consistent with extensive disease. Unfortunately, during her follow-up visits, she presented with bulge on her left eye. Simultaneously, her follow-up chest scan showed increase in the size of the lung nodules. She continued to have a reasonable performance status at that time, except for mild increase in her dyspnea. The choroidal metastases require a multidisciplinary care and should be among the differential patients with malignancy who present with ocular symptoms.

  11. An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    2015-01-01

    Full Text Available The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT and volumetric modulated arc therapy (VMAT for the treatment of nonsmall cell lung cancer (NSCLC. Two partial arcs VMAT, 5-field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV and organs at risk (OARs for hybrid technique was compared with IMRT and VMAT. The monitor units (MUs and treatment delivery time were also evaluated. Hybrid technique significantly improved the target conformity and homogeneity compared with IMRT and VMAT. The mean delivery time of IMRT, VMAT, and hybrid plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT, and hybrid plans were 933, 512, and 737, respectively. Hybrid technique reduced V5, V10, V30, and MLD of normal lung compared with VMAT and spared the OARs better with fewer MUs with the cost of a little higher V5, V10, and mean lung dose (MLD of normal lung compared with IMRT. Hybrid IMRT/VMAT can be a viable radiotherapy technique with better plan quality.

  12. An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer.

    Science.gov (United States)

    Zhao, Nan; Yang, Ruijie; Wang, Junjie; Zhang, Xile; Li, Jinna

    2015-01-01

    The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of nonsmall cell lung cancer (NSCLC). Two partial arcs VMAT, 5-field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for hybrid technique was compared with IMRT and VMAT. The monitor units (MUs) and treatment delivery time were also evaluated. Hybrid technique significantly improved the target conformity and homogeneity compared with IMRT and VMAT. The mean delivery time of IMRT, VMAT, and hybrid plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT, and hybrid plans were 933, 512, and 737, respectively. Hybrid technique reduced V5, V10, V30, and MLD of normal lung compared with VMAT and spared the OARs better with fewer MUs with the cost of a little higher V5, V10, and mean lung dose (MLD) of normal lung compared with IMRT. Hybrid IMRT/VMAT can be a viable radiotherapy technique with better plan quality.

  13. Non-Small Cell Carcinoma Biomarker Testing: The Pathologist's Perspective.

    Directory of Open Access Journals (Sweden)

    Elisa eBrega

    2014-07-01

    Full Text Available Biomarker testing has become standard of care for patients diagnosed with non-small cell lung cancer. Although it can be successfully performed in circulating tu-mor cells, at present, the vast majority of investigations are carried out using di-rect tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically signifi-cant, particularly in cases of lung adenocarcinomas (ADC, which in turn, has prompted a new proposal for the histologic classification of such pulmonary neo-plasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist’s role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire pro-cess happens in a timely fashion. Therefore, it is part of the pathologist’s respon-sibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play NSCLC bi-omarker testing, as well as to provide a summarized review of the main NSCLC bi-omarkers of

  14. 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。

  15. 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.

  16. Afatinib for the treatment of metastatic non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Joshi M

    2015-02-01

    Full Text Available Monika Joshi, Syed M Rizvi, Chandra P Belani Penn State Milton S Hershey Medical Center, Department of Medicine, Division of Hematology-Oncology, Hershey, PA, USA Abstract: Targeting the epidermal growth factor receptor (EGFR in patients with non-small cell lung cancer (NSCLC harboring sensitizing mutations in the tyrosine kinase (TKI domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR exon 19 deletions or exon 21 (L858R substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC. Keywords: afatinib, non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor

  17. Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non-Small Cell Lung Cancer Cells.

    Science.gov (United States)

    Wang, Yiling; He, Jiantao; Zhang, Shenghui; Yang, Qingbo; Wang, Bo; Liu, Zhiyu; Wu, Xintian

    2016-07-13

    Non-small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non-small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non-small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle-associated proteins by Western blot analysis and found immature colon carcinoma transcript 1-mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non-small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non-small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human 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. 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. 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

  2. Metastin is not involved in metastatic potential of non-small cell lung cancer.

    Science.gov (United States)

    Karapanagiotou, Eleni M; Dilana, Kalliopi D; Gkiozos, Ioannis; Gratsias, Ioannis; Tsimpoukis, Sotirios; Polyzos, Aris; Syrigos, Kostas N

    2011-06-01

    Metastin, the product of the KISS-1 gene, seems to represent a strong suppressant of metastasis for some types of cancer. The aim of this study is to explore whether circulating levels of metastin could be used as a marker for the metastatic potential of non-small cell lung cancer (NSCLC) as well as a diagnostic marker in NSCLC patients. The possible correlation between metastin and leptin circulating levels was also evaluated. Fasting serum levels of metastin and leptin were determined in 96 NSCLC patients at diagnosis (76 with metastatic disease and 21 with locally advanced disease) and 49 healthy volunteers using commercial available ELISA. Serum metastin levels presented no differences between NSCLC patients and healthy volunteers (1.18 ± 0.98 vs. 1.17 ± 0.39 ng/ml, P = 0.979) as well as between patients with metastatic and locally advanced disease (1.17 ± 1.05 vs. 1.21 ± 0.64 ng/ml, P = 0.872). There was no statistically significant correlation between circulating metastin and leptin levels in NSCLC patients and patients with locally advanced and metastatic disease. This study shows a lack of direct involvement of metastin in the diagnosis and metastatic potential of NSCLC.

  3. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Paulsen, Birgitte Sandfeld; Aggerholm-Pedersen, N; Bæk, R

    2016-01-01

    BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection...

  4. 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.

  5. 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.

  6. 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.

  7. Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application

    OpenAIRE

    Yuan, Xun; Wu, Hua; Han, Na; Xu, Hanxiao; Chu, Qian; Yu, Shiying; Chen, Yuan; Wu, Kongming

    2014-01-01

    Through epithelial-mesenchymal transition (EMT), cancer cells acquire enhanced ability of migration and invasion, stem cell like characteristics and therapeutic resistance. Notch signaling regulates cell-cell connection, cell polarity and motility during organ development. Recent studies demonstrate that Notch signaling plays an important role in lung cancer initiation and cross-talks with several transcriptional factors to enhance EMT, contributing to the progression of non-small cell lung c...

  8. 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.

  9. 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.

  10. 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。

  11. Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Anagnostou, Valsamo K; Brahmer, Julie R

    2015-03-01

    Emerging evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy even for tumors that were historically considered as nonimmunogenic. Immunotherapy is emerging as a major modality in non-small cell lung cancer (NSCLC) treatment focusing on vaccine approaches to elicit specific immune responses and development of inhibitors of the molecular mediators of cancer-induced immunosuppression (immune checkpoints) to boost antitumor immune responses. Amplification of the host response against evolving tumors through vaccination is being investigated in ongoing clinical trials with tumor cell vaccines; however, the clinical efficacy of these agents has been limited. Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. The activity of immune checkpoint inhibitors is currently been assessed in treatment-naïve patients with PD-L1-positive advanced NSCLC. Combinatorial approaches with other immune checkpoint inhibitors, chemotherapy, or targeted agents are being explored in ongoing clinical trials, and may improve outcome in NSCLC.

  12. MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Debin Ma

    2015-09-01

    Full Text Available MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy.

  13. Survival Analysis of 1,742 Patients with Stage IV Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hong PENG

    2011-04-01

    Full Text Available Background and objective At present non-small cell lung cancer (NSCLC is still the leading cause of death induced by cancer. The aim of this study is to investigate the prognostic factors of advanced NSCLC. Methods Total 1,742 cases of stage IV NSCLC data from Jan 4, 2000 to Dec 25, 2008 in Shanghai Chest Hospital were collected, confirmed by pathological examinations. Analysis was made to observe the impact of treatment on prognosis in gender, age, smoking history, pathology, classification, clinical TNM stage. Survival rate, survival difference were evaluated by Kaplan-Meire method and Logrank test respectively. The prognosis were analyzed by Cox multivariate regression. Results The median survival time of 1,742 patients was 10.0 months (9.5 months-10.5 months. One, two, three, four, and five-year survival rates were 44%, 22%, 13%, 9%, 6% respectively. The median survivals of single or multiple metastasis were 11 months vs 7 months (P < 0.001. Survival time were different in metastasic organs, with the median survival time as follows: lung for about 12 months (11.0 months-12.9 months, bone for 9 months (8.3 months-9.6 months, brain for 8 months (6.8 months-9.1 months, liver, adrenal gland, distannt lymph node metastasis for 5 months (3.8 months-6.1 months, and subcutaneous for 3 months (1.7 months-4.3 months. The median survival times of adenocarcinoma (n=1,086, 62% and squamous cell carcinoma cases (n=305, 17.5% were 12 months vs 8 months (P < 0.001. The median survival time of chemotherapy and best supportive care were 11 months vs 6 months (P < 0.001; the median survival times of with and without radiotherapy were 11 months vs 9 months (P=0.017. Conclusion Gender, age, gross type, pathological type, clinical T stage, N stage, numbers of metastatic organ, smoking history, treatment of advanced non-small cell lung cancer were independent prognostic factors.

  14. Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer.

    Science.gov (United States)

    Nie, Wei; Xu, Mi-die; Gan, Lu; Huang, Hai; Xiu, Qingyu; Li, Bing

    2015-01-01

    Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. However, the clinical significance of STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined. The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect STMN1 protein expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung cancer cell lines was evaluated by small interfering RNA-mediated depletion followed by analyses of cell proliferation and invasion. We found that the STMN1 mRNA and protein levels in NSCLC tissues were significantly higher than those in the corresponding non-tumor tissues (P<0.001). In addition, increased STMN1 expression was correlated with poor tumor differentiation (P<0.001), large tumor size (P=0.022), advanced N stage (P=0.033), and advanced TNM stage (P<0.001). Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression showed significantly worse survival. Moreover, multivariate analysis indicates that higher STMN1 protein expression was an independent prognostic factor of disease-specific survival (HR 2.247, 95%CI 1.320-3.825, P=0.003). Finally, the knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular proliferation and invasion. Our findings suggest that STMN1 may have an important role in NSCLC progression and could serve as a potential prognostic marker for patients with NSCLC.

  15. Mechanisms of Resistance to Target Therapies in Non-small Cell Lung Cancer.

    Science.gov (United States)

    Facchinetti, Francesco; Proto, Claudia; Minari, Roberta; Garassino, Marina; Tiseo, Marcello

    2017-03-23

    Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i.e. MET amplification, KRAS mutations); (3) phenotype transformation (to small cell lung cancer, epithelial-mesenchymal transition). These basic mechanisms are informing the development of novel therapeutic strategies to overcome resistance in the clinic. Novel-generation molecules include osimertinib, for EGFR-T790M-positive patients, and new ALK-TKIs. Nevertheless, the possible concomitant presence of multiple resistance mechanisms, as well as their heterogeneity among cells and disease localizations, makes research in this field particularly arduous. In this chapter, available evidence and perspectives concerning precise mechanisms of escape to pharmacological inhibition in oncogene-addicted NSCLC are reported for single targets, including but not limited to EGFR and ALK.

  16. Characterization of DDR2 Inhibitors for the Treatment of DDR2 Mutated Nonsmall Cell Lung Cancer.

    Science.gov (United States)

    Terai, Hideki; Tan, Li; Beauchamp, Ellen M; Hatcher, John M; Liu, Qingsong; Meyerson, Matthew; Gray, Nathanael S; Hammerman, Peter S

    2015-12-18

    Despite advances in precision medicine approaches over the past decade, the majority of nonsmall cell lung cancers (NSCLCs) are refractory to treatment with targeted small molecule inhibitors. Previous work has identified mutations in the Discoidin Domain Receptor 2 (DDR2) kinase as potential therapeutic targets in NSCLCs. While DDR2 is potently targeted by several multitargeted kinase inhibitors, most notably dasatinib, toxicity has limited the clinical application of anti-DDR2 therapy. Here, we have characterized compound 1 and other tool compounds demonstrating selectivity for DDR2 and show that while these compounds inhibit DDR2 in lung cancer model systems, they display limited antiproliferative activity in DDR2 mutated cell lines as compared to dual DDR2/SRC inhibitors. We show that DDR2 and SRC are binding partners, that SRC activity is tied to DDR2 activation, and that dual inhibition of both DDR2 and SRC leads to enhanced suppression of DDR2 mutated lung cancer cell lines. These results support the further evaluation of dual SRC/DDR2 targeting in NSCLC, and we report a tool compound, compound 5, which potently inhibits both SRC and DDR2 with a distinct selectivity profile as compared to dasatinib.

  17. Non-Small Cell Lung Carcinoma: An Overview on Targeted Therapy.

    Science.gov (United States)

    Nascimento, Ana Vanessa; Bousbaa, Hassan; Ferreira, Domingos; Sarmento, Bruno

    2015-01-01

    Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, most cases are on an advanced and inoperable stage, with limited therapeutic options. Existing therapies have shown to be insufficient and novel strategies are urgently necessary. New advances in understanding the disease at cellular and molecular level however have helped researchers in devising novel strategies for therapy. These directed therapies limit cancer growth by targeting specific molecules related with tumor progression. Such strategies have shown to be more effective than chemotherapy and radiotherapy and can be complemented to existing therapeutic paradigm in augmenting beneficial outcome. Lung cancer could benefit from such innovative therapy. RNA interference (RNAi) is a sequence-specific gene silencing mechanism and, since its discovery widespread applications have pointed it as a powerful tool in cancer treatment. Several on-going clinical trials have been successfully demonstrating its potential as a novel therapeutic, including in the treatment of NSCLC. Here, we revise the recent findings concerning the therapeutic effects of molecular variations associated with NSCLC and where targeted therapies stand in its treatment, with special focus on RNAi-mediated gene silencing as a powerful strategy for NSCLC treatment.

  18. The Evolution of Therapies in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vishal Boolell

    2015-09-01

    Full Text Available The landscape of advanced non-small lung cancer (NSCLC therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR mutations and anaplastic lymphoma kinase (ALK gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs. Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 receptor (PD-1, which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

  19. Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2014-12-01

    Full Text Available The rate of the anaplastic lymphoma kinase (ALK gene rearrangements in non-small cell lung cancer (NSCLC tissues is 3%-5%. The first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802, and AP26113, and new agents shock protein 90 inhibitors. This review aims to present the current knowledge on this fusion gene, the treatment advances, and novel drug clinical trials in ALK rearranged NSCLC.

  20. The Evolution of Therapies in Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Boolell, Vishal, E-mail: vishal.boolell@monashhealth.org.au; Alamgeer, Muhammad [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Watkins, David N. [Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); UNSW Faculty of Medicine, St Vincent’s Clinical School, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Department of Thoracic Medicine, St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Ganju, Vinod [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia)

    2015-09-09

    The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

  1. Surgical treatment of T3 and T4 non-small cell lung cancer

    NARCIS (Netherlands)

    Pitz, Cordula Catharina Maria

    2004-01-01

    The primary goal of lung cancer therapy is complete eradication of the disease. Surgery remains the most curative modality for non-small cell lung cancer. The goal of surgical treatment is to perform a complete resection. Resectability is closely related to the stage of the disease. The thesis focu

  2. PD-L1 expression in non-small cell lung cancer : Correlations with genetic alterations

    NARCIS (Netherlands)

    Scheel, Andreas H.; Ansen, Sascha; Schultheis, Anne M.; Scheffler, Matthias; Fischer, Rieke N.; Michels, Sebastian; Hellmich, Martin; George, Julie; Zander, Thomas; Brockmann, Michael; Stoelben, Erich; Groen, Harry; Timens, Wim; Perner, Sven; von Bergwelt-Baildon, Michael; Buettner, Reinhard; Wolf, Juergen

    2016-01-01

    Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and associat

  3. GENETIC ALTERRATIONS OF MICROSATELLITE MARKERS AT CHROMOSOME 17 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    GUO; Xue-jun

    2001-01-01

    [1]Froudarakis ME, Bouros D, Spandidos DA, et al. Microsatellite instability and loss of heterozygosity at chromosomes 17 in non-small cell lung cancer [J]. Chest 1998; 113:1091.[2]Fong KM, Zimmerman PV, Smith PJ. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer [J]. Cancer Res 1994; 54:2098.[3]Mountain CF. A new international staging system for lung cancer [J]. Chest 1986; 89(suppl):225.[4]Shridhar V, Siegfried J, Hunt J, et al. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas [J]. Cancer Res 1994; 54:2084.[5]Loeb LA. Microsatellite instability: Marker of a mutator phenotype in cancer [J]. Cancer Res 1994; 54:5059.[6]Sanchez CM, Monzo M, Rosell R, et al. Detection of chromosome 3p alterations in serum DNA of non-small cell lung cancer patients [J]. Ann Oncol 1989; 113.

  4. Carcinomatous meningitis in non-small cell lung cancer: Palliation with intrathecal treatment

    Directory of Open Access Journals (Sweden)

    D. Santhosh Kumar

    2014-01-01

    Full Text Available Carcinomatous meningitis or meningeal carcinomatosis is seen in up to 5% of patients of metastatic non-small cell lung cancer. However, isolated carcinomatous meningitis without brain parenchymal metastasis is less common. Patients with carcinomatous meningitis have limited treatment options. However, intrathecal therapy if used optimally along with targeted therapy when indicated result in good palliation with improvement in survival.

  5. Two Cases of Non-Small Cell Lung Cancer Treated with Intravenous Cultivated Wild Ginseng Pharmacopuncture

    Directory of Open Access Journals (Sweden)

    Sun-Hwi Bang

    2008-06-01

    Full Text Available Objectives : To investigate the therapeutic effects of intravenous cultivated wild ginseng(Panax ginseng C.A. Meyer pharmacopuncture(CWGP in treating patients with non-small cell lung cancer(NSCLC. Design : Prospective case series. Setting : This study was conducted at the East-West Cancer Center of Dunsan Oriental Hospital, Daejeon University. Patients : Two non-small cell lung cancer patients. Intervention : Two non-small cell lung cancer patients were injected CWGP(20mL/day mixed with 0.9% normal saline(100mL intravenously. Each patient received a total of 16 and 9 cycles, respectively. One cycle is composed of 14 days. Outcome Measures : The effect of intravenous CWGP was measured by scanning with computed tomography(CT after every 2 cycle and Positron emission tomography- computed tomography(PET/CT after every 6 cycles. Response and progression was evaluated using the Response Evaluation Criteria in Solid Tumors(RECIST Committee classification of complete response(CR, partial response(PR, progressive disease(PD and stable disease(SD. Results : They were treated with intravenous CWGP for 8 and 5 months respectively. time later, each tumor remains stable disease(SD Conclusion : These cases may give us a possibility that intravenous CWGP offers potential benefits for non-small cell lung cancer patients.

  6. Clinical impact of ki-67 labeling index in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Sørensen, Jens Benn

    2013-01-01

    The ki-67 index is a marker of proliferation in malignant tumors. Studies from the period 2000 to 2012 on the prognostic and predictive value of ki-67 labeling index (LI) in non-small cell cancer (NSCLC) are reviewed. Twenty-eight studies reported on the prognostic value of ki-67 index with various...

  7. Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus...

  8. Genome-wide DNA methylation profiling of non-small cell lung carcinomas

    NARCIS (Netherlands)

    R.H. Carvalho (Rejane Hughes); V. Haberle (Vanja); J. Hou (Jun); T. van Gent (Teus); S. Thongjuea (Supat); W.F.J. van IJcken (Wilfred); C. Kockx (Christel); R.W.W. Brouwer (Rutger); E.J. Rijkers; A.M. Sieuwerts (Anieta); J.A. Foekens (John); M. van Vroonhoven (Mirjam); J.G.J.V. Aerts (Joachim); F.G. Grosveld (Frank); B. Lenhard (Boris); J.N.J. Philipsen (Sjaak)

    2012-01-01

    textabstractBackground: Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mechanism of epigenetic regulation involved in normal developm

  9. 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

  10. 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

  11. Synergistic effect of phenformin in non-small cell lung cancer (NSCLC) ionizing radiation treatment.

    Science.gov (United States)

    Wang, Jia; Xia, Shi'an; Zhu, Zhizhen

    2015-03-01

    Biguanides, used for anti-diabetic drugs, bring more attention in cancer research for their beneficial effects. Phenformin is more potent than metformin. However its potential application as a anti-cancer regent is far behind metformin. In order to investigate any beneficial effect of combination of Phenformin and radiotherapy, non-small cell lung cancer cell lines A549 and H1299 were exposure under different dose of ionizing radiation with or without Phenformin. Results indicated Phenformin showed synergistic effect and could induce more cancer cell apoptosis and inhibition of tumor growth compared with ionizing radiation alone. Furthermore, this synergistic effect may be through different pathway according to cancer cell genotype background. Our results showed Phenformin induced AMPK activation in A549 but not H1299. However, Phenformin activated eIF2α in both cell lines. Our findings implicated Phenformin may be used as radiosensitizer for non-small cell lung cancer therapy.

  12. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ko Yoon

    2011-08-01

    Full Text Available Abstract Background CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC. Methods Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82 and squamous cell carcinoma (SCC; n = 77. Additionally, the immunoreactivity of cyclooxygenase (COX-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7% than in those with AC histology (P 0.001. Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021. In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P P = 0.046, and high CD44s expression (P = 0.014. For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015. No significant association was found between CD44s and clinical outcome (P = 0.311. Conclusions High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

  13. 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

  14. The treatment of metastatic non-small cell lung cancer in the elderly: an evidence-based approach

    Directory of Open Access Journals (Sweden)

    David E Dawe

    2014-07-01

    Full Text Available An increasing proportion of patients with advanced NSCLC are over 70 years old, raising unique challenges for treatment decision-making. While these patients are underrepresented in clinical trials, there is an emerging body of evidence associated with this group. The lesson of comprehensive geriatric assessment is that chronological age does not always correlate with physiological age and a variety of important comorbidities and geriatric syndromes can go undetected in a typical history and physical. These comorbidities and expected physiologic changes due to aging complicate decision-making around appropriate treatment. This review discusses geriatric assessment in elderly cancer patients and evaluates the current evidence for chemotherapy and targeted therapy for patients with advanced non-small cell lung cancer aged ≥70 years.

  15. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Peng-hui Zhuang; Zhao-hui Liu; Xiao-gang Jiang; Cheng-en Pan

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKC伪 double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of the 13 cases were double positive for FHIT and PKCα. FHIT protein was present in the immune precipitate of anti-PKCα while there was PKCα in the immune precipitate of anti-FHITmAb. Conclusion FHIT and PKCα exist as a complex in human non-small cell lung cancer tissues, which will provide a new route for studying the pathogenesis and immunotherapy of human non-small cell lung cancer.

  16. Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care

    Science.gov (United States)

    2016-03-01

    Adenocarcinoma of the Lung; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Squamous Cell Lung Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  17. Targeting the PD-1/PD-L1 axis in non-small cell lung cancer.

    Science.gov (United States)

    Kumar, Rajiv; Collins, Dearbhaile; Dolly, Saoirse; McDonald, Fiona; O'Brien, Mary E R; Yap, Timothy A

    2016-12-23

    The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing. Moreover, pembrolizumab has shown a survival advantage in the first-line setting; however, nivolumab failed to show a survival benefit possibly relating to patient selection based on PD-L1 expression. Current patient selection is based on PD-L1 expression, using the relevant companion diagnostic test, where patients with strong PD-L1 expression being more likely to respond to these novel agents. Ongoing clinical research focuses on the development of PD-1 and PD-L1 inhibitor monotherapy in neoadjuvant and adjuvant NSCLC. There is also much interest in using these drugs as a therapeutic backbone for rational combinations with other treatment modalities including cytotoxic chemotherapies in the first-line NSCLC, other immunotherapies such as cytotoxic T-lymphocyte-associated protein 4 antagonists, molecularly targeted agents including EGFR and ALK inhibitors, and radiotherapy. Concurrent treatment with radiotherapy is of particular interest owing to the potential for the abscopal effect, using radiotherapy to facilitate systemic treatment.

  18. 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。

  19. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang, E-mail: brilliant212@163.com; Yang, Xinghai, E-mail: cnspineyang@163.com; Xiao, Jianru, E-mail: jianruxiao83@163.com

    2015-08-21

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

  20. 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。

  1. 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.

  2. 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.

  3. 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.

  4. GENETIC ALTERRATIONS OF MICROSATELLITE MARKERS AT CHROMOSOME 17 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To analyse the microsatellite instability (MI) and loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). Methods: MI and LOH at chromosome 17 were checked in 35 cases of NSCLC tumor-normal paired tissues using four microsatellite markers TP53 (17p13.1), THRA1 (17q11.2-12), D17S579 (17q12-21) and D17S855 (17q21) by PCR based analysis. Mutations of P53 exons 5-8 were also tested using PCR-single strand conformation polymorphism (PCR-SSCP) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis. Results: 22 of 35 tumors (62.8%) displayed MI or LOH. 14 tumors (40.0%) exhibited MI, 11 tumors (31.4%) exhibited LOH, while 3 tumors (8.6%) exhibited MI and LOH concurrently. 23 tumors (65.7%) exhibited P53 gene mutations. The frequency of MI or LOH was obviously higher in the early-stage (stages I and II, 78.9%) than in the advanced-stage (stage III, 43.8%). However, the frequency of MI or LOH had no difference either between high-grade (75.0%) and low-grade (52.6%) differentiated NSCLC or between the tumors with P53 mutations (59.1%) and those without P53 mutations (69.2%). No relationship was observed between the presence of MI or LOH and the histologic subtype of NSCLC. Conclusion: The results suggest that MI and LOH at chromosome 17 may play a alterations on chromosome 17 in tumors of non-small cell lung cancer (NSCLC). In addition, studies reported contradictory results concerning the incidence of these alterations and the relationship between these genetic alterations and the clinical behavior of NSCLC. The aim of this study was to investigate the incidence of MI and LOH at chromosome 17 in tumors of patients with NSCLC and its association with clinical and histologic features of NSCLC.

  5. A RAS renaissance: emerging targeted therapies for KRAS-mutated non-small cell lung cancer.

    Science.gov (United States)

    Vasan, Neil; Boyer, Julie L; Herbst, Roy S

    2014-08-01

    Of the numerous oncogenes implicated in human cancer, the most common and perhaps the most elusive to target pharmacologically is RAS. Since the discovery of RAS in the 1960s, numerous studies have elucidated the mechanism of activity, regulation, and intracellular trafficking of the RAS gene products, and of its regulatory pathways. These pathways yielded druggable targets, such as farnesyltransferase, during the 1980s to 1990s. Unfortunately, early clinical trials investigating farnesyltransferase inhibitors yielded disappointing results, and subsequent interest by pharmaceutical companies in targeting RAS waned. However, recent advances including the identification of novel regulatory enzymes (e.g., Rce1, Icmt, Pdeδ), siRNA-based synthetic lethality screens, and fragment-based small-molecule screens, have resulted in a "Ras renaissance," signified by new Ras and Ras pathway-targeted therapies that have led to new clinical trials of patients with Ras-driven cancers. This review gives an overview of KRas signaling pathways with an emphasis on novel targets and targeted therapies, using non-small cell lung cancer as a case example.

  6. Survival after Pneumonectomy for Stage III Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Sibu P. Saha

    2014-01-01

    Full Text Available Objectives: Stage III non-small cell lung cancer (NSCLC has a poor prognosis. Reports suggest that five-year survival after current treatment is between 14 to 24 percent. The purpose of this retrospective study was to investigate the morbidity and mortality of patients diagnosed with stage III NSCLC and treated with pneumonectomy at the University of Kentucky Medical Center in Lexington, KY. Methods: We reviewed the medical record and tumor registry follow-up data on 100 consecutive patients who underwent pneumonectomy for lung cancer at the University of Kentucky. Results: We identified thirty-six patients in stage III who underwent pneumonectomy. Ten patients had surgery only, eight patients received adjuvant chemotherapy, and eighteen patients received neoadjuvant therapy. There was one surgical death in this series. Mean follow-up was 2.9 years. One-, three-, and five-year survival was 66%, 38%, and 38%, respectively. Five-year survival for the group with adjuvant therapy was 60%. Conclusion: Most lung cancer patients present with advanced disease and the prognosis remains poor. Our experience indicates resection offers an above average chance of long-term survival when supplemented with neoadjuvant and/or adjuvant therapy.

  7. Interpretation of NCCN Guidelines: General Therapies on Non-small Cell Lung Cancer (Version 6. 2015

    Directory of Open Access Journals (Sweden)

    Xin-en HUANG

    2015-06-01

    Full Text Available Lung cancer is one of the most common malignant tumors in China and ranks the first of cancer-related death. The major etiological agent of lung cancer is an industry-made and promoted addictive product, so lung cancer is considered to be a unique disease in all cancers. Effective policies for public health are required to prevent the smoking initiation so as to reduce the mortality of lung cancer, so Food and Drug Administration (FDA has introduced a series of measures to monitor the tobacco products. As to patients with strong suspicion of lung cancer in stage Ⅰ-Ⅱ, a preoperative biopsy is needed and intra-operative diagnosis is necessary before pneumonectomy, bilobectomy or lobectomy if the preoperative tissue diagnosis is not obtained. However, lung cancer still cannot be easily diagnosed and cured, so the annual improvement and update of new therapeutic protocols and the development of new agents is of great significance. Non-small cell lung cancer (NSCLC accounts for about 80% of all lung cancer, and above 75% NSCLC patients are in middle-advanced stage when diagnosed, so they have lost the optimal therapeutic opportunity and the 5-year survival rate is relatively low. Therefore, this study mainly interpreted the National Comprehensive Cancer Network (NCCN guidelines on the general therapies on NSCLC, hoping to provide references for the treatment of NSCLC patients and prolong their long-term survival.

  8. Non-small cell lung cancer therapy: safety and efficacy in the elderly

    Directory of Open Access Journals (Sweden)

    Glotzer OS

    2013-04-01

    Full Text Available Owen S Glotzer,1 Thomas Fabian,1 Anurag Chandra,2 Charles T Bakhos21Division of Thoracic Surgery, Albany Medical Center, Department of Surgery, Albany Medical College, Albany, New York, USA; 2Department of Radiation Oncology, Albany Medical Center, Albany Medical College, Albany, New York, USABackground: Our objective was to evaluate and review the current literature on the treatment of non-small cell lung cancer (NSCLC in the elderly.Methods: We selected recent peer-reviewed articles addressing ageing, cancer treatment in the elderly, and lung cancer treatment in the elderly. We defined elderly as over the age of 70.Results: The population is ageing dramatically throughout most of the world. Given that situation, clinicians are seeing and being asked to treat more elderly patients that have NSCLC. Elderly patients are less likely to participate or be allowed to participate in prospective or retrospective studies of treatments for NSCLC. Elderly patients are also less likely to be staged appropriately for their advanced tumors, and are less likely to be referred for surgery or adjuvant therapy after surgery. When treatment is tailored to patient comorbidities but not to age, the data support survival and outcomes comparable to those of younger patients.Conclusions: Data are limited on the treatment of elderly patients with NSCLC. No data exist to support limiting recommendations for treatment based on age alone. Treatments should be determined on an individual basis.Keywords: thoracic surgery, radiation therapy, chemotherapy, pulmonary, physiology, ageing, SBRT

  9. Targeted Therapies in Non-Small Cell Lung Cancer—Beyond EGFR and ALK

    Directory of Open Access Journals (Sweden)

    Sacha I. Rothschild

    2015-05-01

    Full Text Available Systemic therapy for non-small cell lung cancer (NSCLC has undergone a dramatic paradigm shift over the past decade. Advances in our understanding of the underlying biology of NSCLC have revealed distinct molecular subtypes. A substantial proportion of NSCLC depends on oncogenic molecular aberrations (so-called “driver mutations” for their malignant phenotype. Personalized therapy encompasses the strategy of matching these subtypes with effective targeted therapies. EGFR mutations and ALK translocation are the most effectively targeted oncogenes in NSCLC. EGFR mutations and ALK gene rearrangements are successfully being targeted with specific tyrosine kinase inhibitors. The number of molecular subgroups of NSCLC continues to grow. The scope of this review is to discuss recent data on novel molecular targets as ROS1, BRAF, KRAS, HER2, c-MET, RET, PIK3CA, FGFR1 and DDR2. Thereby the review will focus on therapeutic strategies targeting these aberrations. Moreover, the emerging challenge of acquired resistance to initially effective therapies will be discussed.

  10. Effect of lumiracoxib on proliferation and apoptosis of human nonsmall cell lung cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    HAO Ji-qing; LI Qi; XU Shu-ping; SHEN Yu-xian; SUN Gen-yun

    2008-01-01

    Background Lumiracoxib is a highly selective cyclooxygenase-2(COX-2)inhibitor with antiinflammatory,analgesic and antipyretic activities comparable with class specific drugs,but with much improved gastrointestinal safety.No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Drug-drug interactions were analyzed using the coefficient of drug interaction(CDI)to characterize the interactions as synergism,additivity or antagonism.Morphological changes were observed by acridine orange fluorescent staining.Extent of apoptosis was determined by flow cytometry.Results Lumiracoxib(15-240 μmol/L)has an inhibitory effect on the proliferation of A549 and NCI-H460 celllines in concentration- and time-dependent manners with the IC50 values of 2597 μmol/L and 833 pmol/L,respectively.The synergistic effect was prominent when lumiracoxib(15-240 μmol/L)was combined with docetaxol(0.2-2 μmol/L)(CDI <1).Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells.Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol,which may be related to apoptotic induction and cell cycle arrest.

  11. Detection of circulating tumor cells in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Annkathrin eHanssen

    2015-09-01

    Full Text Available Lung Cancer is the most common cause of cancer related deaths that frequently metastasizes prior to disease diagnosis. Circulating tumor cells (CTCs are found in many different types of epithelial tumors and are of great clinical interest in terms of prognosis and therapy intervention. Here, we present and discuss EpCAM-dependent and -independent capture of CTCs in non-small cell lung cancer (NSCLC and the clinical relevance of CTC detection and characterization. Taking blood samples and analyzing CTCs as liquid biopsy might be a far less invasive diagnostic strategy than biopsies of lung tumors or metastases. Moreover, sequential blood sampling allows to study the dynamic changes of tumor cells during therapy, in particular the development of resistant tumor cell clones.

  12. 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.

  13. [Suppression of WIFI transcript and protein in non-small cell lung carcinomas].

    Science.gov (United States)

    Korobko, E V; Kalinichenko, S V; Shepelev, M V; Zborovskaia, I B; Allakhverdiev, A K; Zinov'eva, M V; Vinogradova, T V; Sverdlov, E D; Korobko, I V

    2007-01-01

    Changes in WIFI expression, an extracellular inhibitor of Wnt pathway, in non-small cell lung carcinomas were analyzed. Frequent (67% cases) suppression of WIFI transcript in non-small cell lung carcinomas were found. Our results, together with previously published data, suggest that inhibition of WIFI expression often occurs in squamous cell carcinomas and is less typical of adenocarcinomas. It was also found that a decrease in the WIFI transcript in tumors is parallel to concomitant suppression of the WIFI protein level. Our results provide further evidence that the WIFI suppression is a frequent event in the lung carcinogenesis, which might lead to disregulation of Wnt signaling pathway and contribute to tumor progression.

  14. 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

  15. 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

  16. Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review).

    Science.gov (United States)

    Zinner, Ralph; Visseren-Grul, Carla; Spigel, David R; Obasaju, Coleman

    2016-01-01

    Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included 'pemetrexed,' 'NSCLC' and 'PS2'. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed‑carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; Pstudies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed.

  17. Evaluation of Three Small Molecular Drugs for Targeted Therapy to Treat Nonsmall Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Ni; Li Zhang

    2016-01-01

    Objective: To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in clinical practice.This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib,erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.Data Sources: An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib,icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.Study Selection: The search terms or keywords included but not limited to "lung cancer", "nonsmall cell lung cancer (NSCLC)","epidemiology", "EGFR", "TKIs", and "optimal selection".Results: As suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain.The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food.The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage.Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food.Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment.In marked contrast, icotinib is available only in China as the second-or third-line therapeutic approach for treating advanced lung cancer.In addition, it exhibits a similar efficacy but better safety profile than gefitinib.Conclusions: Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with

  18. Cell proliferation and apoptosis in stage III inoperable non-small cell lung carcinoma treated by radiotherapy

    NARCIS (Netherlands)

    Langendijk, H; Thunnissen, E; Arends, JW; de Jong, J; ten Velde, G; Lamers, R; Guinee, D; Holden, J; Wouters, M

    2000-01-01

    Purpose: The purpose of this study was to assess the prognostic value of the expression of p53 and bcl-2, the apoptotic index and the expression of topoisomerase II alpha in patients with inoperable non-small cell lung cancer (NSCLC) treated with high dose radiotherapy. Patients and methods: A numbe

  19. Progesterone and estrogen receptor expression and activity in human non-small cell lung cancer

    OpenAIRE

    2011-01-01

    Lung cancer is the most common cause of cancer mortality in male and female patients in the US. Although it is clear that tobacco smoking is a major cause of lung cancer, about half of all women with lung cancer worldwide are never-smokers. Despite a declining smoking population, the incidence of non-small cell lung cancer (NSCLC), the predominant form of lung cancer, has reached epidemic proportions particularly in women. Emerging data suggest that factors other than tobacco, namely endogeno...

  20. Simulating non-small cell lung cancer with a multiscale agent-based model

    OpenAIRE

    Deisboeck Thomas S; Sagotsky Jonathan; Zhang Le; Wang Zhihui

    2007-01-01

    Abstract Background The epidermal growth factor receptor (EGFR) is frequently overexpressed in many cancers, including non-small cell lung cancer (NSCLC). In silico modeling is considered to be an increasingly promising tool to add useful insights into the dynamics of the EGFR signal transduction pathway. However, most of the previous modeling work focused on the molecular or the cellular level only, neglecting the crucial feedback between these scales as well as the interaction with the hete...

  1. Optimal Therapeutic Strategy for Non-small Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor

    Directory of Open Access Journals (Sweden)

    Zhong SHI

    2015-02-01

    Full Text Available Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in non-small cell lung cancer (NSCLC patients, it is still controversial about how to combine EGFR-TKI with chemotherapy and other targeted drugs. We have made a summary on the current therapeutic models of EGFR-TKI combined with chemotherapy/bevacizumab in this review and aimed to find the optimal therapeutic strategy for NSCLC patients with EGFR mutation.

  2. Living with a diagnosis of non-small cell lung cancer: patients' lived experiences.

    LENUS (Irish Health Repository)

    McCarthy, Ita

    2012-01-31

    The aim of this study was to explore patients\\' experience of living with non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC know that their treatment is not with curative intent and can expect distressing symptoms. In this phenomenological study, six adults with a diagnosis of NSCLC were interviewed. Data was analysed guided by van Manen\\'s six-step process. Four main themes were interpreted: \\'Maintaining my life\\'; \\'The enemy within\\'; \\'Staying on the train\\

  3. 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.

  4. 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

  5. PTRF/Cavin-1 and MIF Proteins Are Identified as Non-Small Cell Lung Cancer Biomarkers by Label-Free Proteomics

    Science.gov (United States)

    Gámez-Pozo, Angelo; Sánchez-Navarro, Iker; Calvo, Enrique; Agulló-Ortuño, María Teresa; López-Vacas, Rocío; Díaz, Esther; Camafeita, Emilio; Nistal, Manuel; Madero, Rosario; Espinosa, Enrique; López, Juan Antonio; Vara, Juan Ángel Fresno

    2012-01-01

    With the completion of the human genome sequence, biomedical sciences have entered in the “omics” era, mainly due to high-throughput genomics techniques and the recent application of mass spectrometry to proteomics analyses. However, there is still a time lag between these technological advances and their application in the clinical setting. Our work is designed to build bridges between high-performance proteomics and clinical routine. Protein extracts were obtained from fresh frozen normal lung and non-small cell lung cancer samples. We applied a phosphopeptide enrichment followed by LC-MS/MS. Subsequent label-free quantification and bioinformatics analyses were performed. We assessed protein patterns on these samples, showing dozens of differential markers between normal and tumor tissue. Gene ontology and interactome analyses identified signaling pathways altered on tumor tissue. We have identified two proteins, PTRF/cavin-1 and MIF, which are differentially expressed between normal lung and non-small cell lung cancer. These potential biomarkers were validated using western blot and immunohistochemistry. The application of discovery-based proteomics analyses in clinical samples allowed us to identify new potential biomarkers and therapeutic targets in non-small cell lung cancer. PMID:22461895

  6. PTRF/cavin-1 and MIF proteins are identified as non-small cell lung cancer biomarkers by label-free proteomics.

    Directory of Open Access Journals (Sweden)

    Angelo Gámez-Pozo

    Full Text Available With the completion of the human genome sequence, biomedical sciences have entered in the "omics" era, mainly due to high-throughput genomics techniques and the recent application of mass spectrometry to proteomics analyses. However, there is still a time lag between these technological advances and their application in the clinical setting. Our work is designed to build bridges between high-performance proteomics and clinical routine. Protein extracts were obtained from fresh frozen normal lung and non-small cell lung cancer samples. We applied a phosphopeptide enrichment followed by LC-MS/MS. Subsequent label-free quantification and bioinformatics analyses were performed. We assessed protein patterns on these samples, showing dozens of differential markers between normal and tumor tissue. Gene ontology and interactome analyses identified signaling pathways altered on tumor tissue. We have identified two proteins, PTRF/cavin-1 and MIF, which are differentially expressed between normal lung and non-small cell lung cancer. These potential biomarkers were validated using western blot and immunohistochemistry. The application of discovery-based proteomics analyses in clinical samples allowed us to identify new potential biomarkers and therapeutic targets in non-small cell lung cancer.

  7. A Pilot Study of Circulating Tumor Cells in Stage IV Non-Small Cell Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Max Haid

    2016-08-01

    Full Text Available Purpose: Measurement of the number of circulating tumor cells (CTCs in the bloodstream has been shown to have prognostic significance in treating breast carcinoma. This pilot study was formulated to determine if stage IV non-small cell lung carcinomas similarly shed malignant cells into the circulation and if their presence has prognostic significance. Methods: Patients with stage IV non-small cell lung carcinomas were tested once for CTCs in 7.5 ml of their blood prior to receiving any treatments. A proprietary blood collection kit produced by Veridex LLC (Raritan, NJ, which manufactures the instrument that performs the immunomagnetic CELLSEARCH® CTC assay, was used. Tumor measurements were determined in three dimensions by the same radiologist using computerized axial tomography. The three-dimensional sum was used to represent tumor size. Survival from the date of the pretreatment CTC assay was monitored and recorded. Data were analyzed statistically using NCSS8 statistical software (NCSS LLC, Kaysville, UT. Results: Of 19 evaluable patients, 10 had no detectable CTCs. There was no relation between intrapulmonary primary tumor size and the number of CTCs, nor between tumor size and survival. Survival was not affected by gender or age at entry into the trial. The mean survival of those with no detectable CTCs was 536 ± 91.1 days versus 239 ± 96.0 days for those with 1 or more detectable CTCs, a statistically significant advantage (P=0.034 favoring those without CTCs. Conclusions: Patients with a CTC score of 0 survived significantly longer than those with a CTC score of ≥ 1. Survival was not correlated with gender, age or primary tumor size. Recovery of CTCs potentially provides a noninvasive source of tumor cells for genomic profiling, which may enable development of a custom treatment plan for the individual patient. Further investigations are warranted and needed.

  8. Overexpression of cyclin Y in non-small cell lung cancer is associated with cancer cell proliferation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Cyclin Y (CCNY) is a key cell cycle regulator that acts as a growth factor sensor to integrate extracellular signals with the cell cycle machinery. The expression status of CCNY in lung cancer and its clinical significance remain unknown. The data indicates that CCNY may be deregulated in non-small cell lung cancer, where it may act to promote cell proliferation. These studies suggest that CCNY may be a candidate biomarker of NSCLC and a possible therapeutic target for lung cancer treatment.

  9. 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.

  10. A Rare Case of Non-Small Cell Carcinoma of Lung Presenting as Miliary Mottling

    Directory of Open Access Journals (Sweden)

    Ballaekere Jayaram Subhashchandra

    2013-03-01

    Full Text Available Miliary mottling on chest radiography is seen in miliary tuberculosis, certain fungal infections, sarcoidosis, coal miner’s pneumoconiosis, silicosis, hemosiderosis, fibrosing alveolitis, acute extrinsic allergic alveolitis, pulmonary eosinophilic syndrome, pulmonary alveolar proteinosis, and rarely in hematogenous metastases from the primary cancers of the thyroid, kidney, trophoblasts, and some sarcomas. Although very infrequent, miliary mottling can be seen in primary lung cancers. Herein, we report the case of a 28-year-old female with chest X-ray showing miliary mottling. Thoracic computed tomography (CT features were suggestive of tuberculoma with miliary tuberculosis. CT-guided fine needle aspiration cytology confirmed the diagnosis as lower-lobe, left lung non-small cell carcinoma (adenocarcinoma. It is rare for the non-small cell carcinoma of the lung to present as miliary mottling. The rarity of our case lies in the fact that a young, non-smoking female with miliary mottling was diagnosed with non-small cell carcinoma of the lung.

  11. 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

  12. 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

  13. 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

  14. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era.

    Science.gov (United States)

    Remon, J; Le Rhun, E; Besse, B

    2017-02-01

    Leptomeningeal metastasis is a fatal manifestation seen in advanced cancer patients. Its incidence is increasing, reaching 3.8% in molecularly unselected non-small cell lung cancer patients and up to 5% and 9% in ALK-rearranged and EGFR-mutant lung cancer patients, respectively. The prognosis remains poor despite systemic treatment, intrathecal chemotherapy, radiation therapy and personalized treatments in molecularly selected patients. However, new therapies with improved cerebral-spinal fluid penetration have been developed for subgroups of molecular selected patients indicating they could be promising therapeutic options for managing leptomeningeal disease. Systemic chemotherapy, which may be combined with intrathecal chemotherapy, remains standard treatment for lung cancer patients with leptomeningeal disease and a good-risk profile. We summarize evidence reported in the literature for managing this complication in lung cancer patients. Based on this, we have selected potential therapeutic strategies that could be used in daily clinical practice.

  15. A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

    2016-12-01

    Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic.

  16. A Systemic Review of Resistance Mechanisms and Ongoing Clinical Trials in ALK-rearranged Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Khashayar eEsfahani

    2014-07-01

    Full Text Available The identification of oncogenic driver driver mutations in non-small cell lung cancer has led to a paradigm shift and the development of specific molecular treatments. Tumors harboring a rearranged EML4-ALK fusion oncogene are highly sensitive to therapy with ALK-targeted inhibitors. Crizotinib is the first approved treatment for advanced lung tumors containing this genetic abnormality. In this mini review, we discuss the existing data on crizotinib as well as ongoing trials involving this medication. A brief overview of the known resistance mechanisms to criztotinib will also be presented followed by a summary of the ongoing trials involving next-generation ALK inhibitors or other targeted therapies in patients with ALK+ NSCLC.

  17. 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.

  18. 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

    Directory of Open Access Journals (Sweden)

    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

  19. 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.

  20. Research Progress of the Resistance Mechanism of Non-small Cell Lung Cancer 
to EGFR-TKIs

    Directory of Open Access Journals (Sweden)

    Huihui LIU

    2013-10-01

    Full Text Available Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC makes up about 80%. There is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. The standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. Then exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs have achieved a great success in the treatment of advanced NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, after a period of treatment (median time is 6 to 12 months, most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs: primary and acquired resistances. The research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. The aim of this article was to summarize the development of the resistance mechanisms.

  1. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Lincan [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Shen, Hongmei [Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhao, Guangqiang [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Yang, Runxiang [Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Cai, Xinyi [Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhang, Lijuan [Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Jin, Congguo [Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Huang, Yunchao, E-mail: daliduanlincan@163.com [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  2. Inhibition of TRPC6 reduces non-small cell lung cancer cell proliferation and invasion

    Science.gov (United States)

    Lu, Xiao-Yu; Yan, Yan; Zhai, Yu-Jia; Bao, Qing; Doetsch, Paul W.; Deng, Xingming; Thai, Tiffany L.; Alli, Abdel A.; Eaton, Douglas C.; Shen, Bao-Zhong; Ma, He-Ping

    2017-01-01

    Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death. Western blot and cell cycle analysis show that the detached round cells at the S-G2M phase expressed more TRPC6 than the still attached polygon cells at the G1 phase. Patch-clamp data also show that TRPC whole-cell currents in the detached cells were significantly higher than in the still attached cells. Inhibition of Ca2+-permeable TRPC6 channels significantly reduced intracellular Ca2+ in A549 cells. Interestingly, either blockade or knockdown of TRPC6 strongly reduced the invasion of this NSCLC cell line and decreased the expression of an adherent protein, fibronectin, and a tight junction protein, zonula occluden protein-1 (ZO-1). These data suggest that TRPC6-mediated elevation of intracellular Ca2+ stimulates NSCLC cell proliferation by promoting cell cycle progression and that inhibition of TRPC6 attenuates cell proliferation and invasion. Therefore, further in vivo studies may lead to a consideration of using a specific TRPC6 blocker as a complement to treat NSCLC. PMID:28030826

  3. 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。

  4. Autophagy Accompanied with Bisdemethoxycurcumin-induced Apoptosis in Non-small Cell Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    XU Jin Hong; YANG He Ping; ZHOU Xiang Dong; WANG Hai Jing; GONG Liang; TANG Chun Lan

    2015-01-01

    Objective To investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells. Methods CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells. Results BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells (SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened (SMO) and the transcription factor glioma-associated oncogene 1 (Gli1) expression. Furthermore, depletion of Gli1 by siRNA and cyclopamine (a specific SMO inhibitor) induced autophagy. Conclusion Aberrant activation of Hedgehog (Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.

  5. Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    SUN Bing-sheng; YOU Jian; LI Yue; ZHANG Zhen-fa; WANG Chang-li

    2013-01-01

    Background Osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of malignant tumor.However,the mechanism by which OPN mediates metastasis in non-small cell lung cancer (NSCLC) remains unknown.The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line.Methods Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic human NSCLC cell line (A549).The invasion,proliferation,and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo.The related mechanism was further investigated.Results Interestingly,OPN knockdown significantly suppressed the invasiveness of A549 cells,but had only a minor effect on the cellular migration and proliferation.Moreover,we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA),and led to an obviousinhibition of both in vitro invasion and in vivo lung metastasis of A549 cells (P <0.001).Conclusions Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion,independent of cellular migration and proliferation.OPN could be a new treatment target of NSCLC.

  6. 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

  7. Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Amit Dutt

    Full Text Available BACKGROUND: Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes-WHSC1L1, LETM2, and FGFR1-is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. CONCLUSIONS/SIGNIFICANCE: These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.

  8. Unlocking Pandora's box: personalising cancer cell death in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Fennell Dean A

    2012-06-01

    Full Text Available Abstract Evasion of apoptosis is a hallmark of tumorigenesis and a recognised cause of multidrug resistance. Over the last decade, insights into how apoptosis might be exploited in non-small cell lung cancer (NSCLC and how cancer therapeutics might be used to engage apoptotic signalling in a personalised manner have changed markedly. We are now in the wake of a paradigm shift in stratified therapeutic approaches related to NSCLC. At the heart of this shift in thinking is the emerging knowledge that even the most drug-resistant cancers exhibit a functional death pathway and, critically, that this pathway can be efficiently engaged, leading to clinical benefit. This review will summarise current knowledge of mitochondrial apoptotic pathway dysfunction in NSCLC and how the next generation of targeted therapeutics might be used to exploit deficiencies in apoptotic signalling in a personalised manner to improve clinical outcome and predict therapeutic benefit.

  9. miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells.

    Science.gov (United States)

    Chen, Gang; Umelo, Ijeoma Adaku; Lv, Shasha; Teugels, Erik; Fostier, Karel; Kronenberger, Peter; Dewaele, Alex; Sadones, Jan; Geers, Caroline; De Grève, Jacques

    2013-01-01

    Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to various aspects of the malignant phenotype of human NSCLCs. In functional experiments, miR-146a suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292). miR-146a also inhibited the migratory capacity of these NSCLC cells. On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab). These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR. Our results suggest that these effects of miR-146a are due to its targeting of EGFR and NF-κB signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE) lung cancer samples, that low expression of miR-146a was correlated with advanced clinical TNM stages and distant metastasis in NSCLC (Pstrategy for NSCLC.

  10. Noncoding RNA small nucleolar RNA host gene 1 promote cell proliferation in nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    J You

    2014-01-01

    Full Text Available Background: Nonsmall cell lung cancer (NSCLC is the major cause of cancer death worldwide. Increasing evidence shows that noncoding RNAs (ncRNAs are widely involved in the development and progression of NSCLC. ncRNA small nucleolar RNA host gene 1 (SNHG1 has not been studied in cancer, especially its role in lung cancer remains unknown. Our studies were designed to investigate the expression and biological significance of SNHG1 in lung cancer. SNHG1 may be a novel ncRNA in early diagnosis in lung cancer. Methods: Noncoding RNA SNHG1 expression in 7 lung cancer cell lines was measured by quantitative real-time polymerase chain reaction. RNA interference approaches were used to find the biological functions of SNHG1. The effect of SNHG1 on proliferation was evaluated by cell count and crystal violet stains. Results: Noncoding RNA SNHG1 expression was significantly upregulated in lung cancer cells when compared with normal bronchial epithelial cells. In addition, in vitro assays our results indicated that knockdown of SNHG1 inhibited cell proliferation. Conclusions: Our data indicated that ncRNA SNHG1 is significantly upregulated in NSCLC cell lines and may represent a new biomarker and a potential therapeutic target for NSCLC intervention.

  11. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells.

    Science.gov (United States)

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  12. 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。

  13. 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

  14. Tolerability and toxicity of adjuvant cisplatin and gemcitabine for treating non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    YANG Fan; LI Xiao; CHEN Ke-zhong; JIANG Guan-chao; WANG Jun

    2013-01-01

    Background The combination of cisplatin and vinorelbine is an evidence-supported regimen for adjuvant chemotherapy for treating non-small cell lung cancer (NSCLC).But this doublet has considerable toxicity and unfavorable tolerability,and results in poor compliance.The cisplatin and gemcitabine regimen is one of the most active and well-tolerated regimens against advanced NSCLC,but its toxicity and tolerability has not been adequately evaluated in the adjuvant setting.Methods From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m2) and gemcitabine (1250 mg/m2) between January 2005 and December 2011.Postoperative demographics,compliance to adjuvant therapy and toxicity were retrieved from medical records.Results A total of 132 patients met the criteria and were included in the study,96 were male (72.7%) and 36 were female (27.3%).Median age was 60.5 years old,range 29-75 years,and 41.7% of patients were ≥65 years old.Overall,68.2%patients received all four planned cycles,and the cumulative dose delivered for gemcitabine was 8333 mg (83.3% of the planned dose) and cisplatin 248 mg (82.7% of the planned dose).There were no treatment-related deaths.Grade 3/4neutropenia developed in 47 patients (35.6%) and was the predominant hematologic toxicity.Common grade 3/4 nonhematologic toxicities were nausea/vomiting (22.0%),infection (12.3%),and febrile neutropenia (11.4%).Conclusion Cisplatin and gemcitabine are feasible for use in the adjuvant setting with a favorable toxicity profile and superior tolerability compared with published data on cisplatin and vinorelbine.

  15. Dietary Flaxseed in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation

    Science.gov (United States)

    Berman, Abigail T; Turowski, Jason; Mick, Rosemarie; Cengel, Keith; Farnese, Nicole; Basel-Brown, Lisa; Mesaros, Clementina; Blair, Ian; Lawson, James; Christofidou-Solomidou, Melpo; Lee, James; Rengan, Ramesh

    2013-01-01

    Purpose The standard of care in Locally-Advanced Non-Small Cell Lung Cancer (LA-NSCLC) is chemotherapy and radiation; however, Radiation-Induced Lung Injury (RILI), which may be prevented by the anti-inflammatory and anti-oxidant properties of Flaxseed (FS), impedes its maximum benefit. Materials and Methods Patients with LA-NSCLC requiring definitive RT were randomized to one FS or control muffin daily from start to 2 weeks after RT. Blood and urine were collected to quantify plasma FS metabolites, Enterodione (ED) and Enterolactone (EL), and urinary oxidative stress biomarkers, 8, 12-iso-iPF2a-VI (isoprostane) and 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxo-dGuo). Tolerability was defined as consuming ≥ 75% of the intended muffins and no ≥ grade 3 gastrointestinal toxicities. Results Fourteen patients (control,7; FS,7) were enrolled. The tolerability rates were 42.9 versus 71.4% (p=0.59) for FS and control, respectively. Mean percentages of intended number of muffins consumed were 37% versus 73% (p=0.12). ED and EL increased at onset of FS and decreased with discontinuation, confirming bioavailability. Isoprostane and 8-oxo-dGuo were detectable. There was a trend towards decreased rates of pneumonitis in FS. Conclusions This is the first study to report FS bioavailability and quantify oxidative stress markers in NSCLC patients. FS in the administered muffin formulation did not meet tolerability criteria. Given the promising mechanism of FS as a radioprotectant, further investigations should focus on the optimal method for administration of FS. PMID:24575360

  16. DNA Repair Gene Polymorphisms in Relation to Non-Small Cell Lung Cancer Survival

    Directory of Open Access Journals (Sweden)

    Yuliang Su

    2015-07-01

    Full Text Available Background: Single nucleotide polymorphisms (SNPs in the DNA repair genes are suspected to be related to the survival of lung cancer patients due to their possible influence on DNA repair capacity (DRC. However, the study results are inconsistent. Methods: A follow-up study of 610 non-small cell lung cancer (NSCLC patients was conducted to investigate genetic polymorphisms associated with the DNA repair genes in relation to NSCLC survival; 6 SNPs were genotyped, including XRCC1 (rs25487 G>A, hOGG1 (rs1052133 C>G, MUTYH (rs3219489 G>C, XPA (rs1800975 G>A, ERCC2 (rs1799793 G>A and XRCC3 (rs861539 C>T. Kaplan-Meier survival curve and Cox proportional hazards regression analyses were performed. SNP-SNP interaction was also examined using the survival tree analysis. Results: Advanced disease stage and older age at diagnosis were associated with poor prognosis of NSCLC. Patients with the variant ‘G' allele of hOGG1 rs1052133 had poor overall survival compared with those with the homozygous wild ‘CC' genotype, especially in female patients, adenocarcinoma histology, early stage, light smokers and without family history of cancer. For never smoking female lung cancer patients, individuals carrying homozygous variant ‘AA' genotype of XPA had shorter survival time compared to those with wild ‘G' alleles. Furthermore, females carrying homozygous variant XPA and hOGG1 genotypes simultaneously had 2.78-fold increased risk for death. Among all 6 polymorphisms, the homozygous variant ‘AA' of XPA carriers had poor prognosis compared to the carriers of wild ‘G' alleles of XPA together with other base excision repair (BER polymorphisms. Conclusions: Besides disease stage and age, the study found DNA repair gene polymorphisms were associated with lung cancer survival.

  17. 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.

  18. 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.

  19. 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.

  20. Advanced Cell Technology, Inc.

    Science.gov (United States)

    Caldwell, William M

    2007-03-01

    Advanced Cell Technology, Inc. (OTCBB: ACTC) is a biotechnology company applying novel human embryonic stem cell technologies in the emerging field of regenerative medicine. We believe that regenerative medicine has the potential to revolutionize the field by enabling scientists to produce human cells of any kind for use in a wide array of therapies.

  1. [Clinical significance of cyclin Dl expression in non-small cell lung cancer].

    Science.gov (United States)

    Dworakowska, Dorota

    2005-01-01

    Lung cancer remains interdisciplinary problem. The genetic alterations in non-small cell lung cancer (NSCLC) are related to tumor suppressor genes and proto-oncogenes. CCND1 gene, coding cyclin DI, in correlation with pRb is involved in regulation of cell cycle arrest in G1 phase. Amplification of CCND1 gene and cyclin D1 over-expression was found in several cancers including head and neck cancers or colorectal cancer, where these alterations were correlated with worse prognosis. The literature addressing the clinical significance of CCND1 gene amplification/expression in NSCLC remains poor and prognostic value of these alterations in that cancer is still controversial.

  2. SKA1 regulates the metastasis and cisplatin resistance of non-small cell lung cancer

    Science.gov (United States)

    SHEN, LIHUA; YANG, MIN; LIN, QIONGHUA; ZHANG, ZHONGWEI; MIAO, CHANGHONG; ZHU, BIAO

    2016-01-01

    Currently, chemotherapy with platinum-based drugs including cisplatin is the most effective therapy for the treatment of non-small cell lung carcinoma (NSCLC). However, the efficacy of chemotherapy is limited due to commonly developed drug resistance. Spindle and kinetochore-associated complex subunit 1 (SKA1) is part of a complex essential for stabilizing the attachment of spindle microtubules to kinetochores and for maintaining the metaphase plate during mitosis. In the present study, we aimed to investigate the role of SKA1 in the process of metastasis and drug resistance of NSCLC. We completed a series of experiments to investigate the function of SKA1 in NSCLC metastasis and drug resistance including qRT-PCR, immunohistochemistry and western blotting, as well as MTT, BrdU, wounded healing, Transwell and gelatin zymography assays. We demonstrated that the expression levels of SKA1 were elevated in NSCLC and were correlated with cancer progression and malignancy. We also reported that SKA1 positively regulated the proliferation and metastatic ability of NSCLC cells. In addition, we determined that SKA1 contributed to cisplatin resistance in NSCLC cells by protecting these cells from cisplatin-induced cell apoptosis. SKA1 also appeared to regulate the ERK1/2 and the Akt-mediated signaling pathways in NSCLC cells. SKA1 is required for metastasis and cisplatin resistance of non-small cell lung cancer. PMID:26985856

  3. Comparison of therapeutic effects between EGFR-TKI in first-line and second-line therapy in non-small cell lung cancer (NSCLC) patients

    OpenAIRE

    CHEN, LIANG-AN

    2011-01-01

    Platinum-based chemotherapy is still the standard first-line treatment for patients with advanced non-small cell lung cancer(NSCLC).Molecular targeted agents provide a new option for NSCLC patients.Clinical trial had shown that survival rate with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) treatment was not inferior compared with platinum-based chemotherapy in second line NSCLC therapy.However,for the patients with EGFR gene mutation,a better outcome has been achieved...

  4. Research Progress of Epidermal Growth Factor Receptor and Molecular-Targeted Therapy in Treatment of Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoyou Li

    2014-03-01

    Full Text Available Molecular target therapy has become a new approach in the treatment of advanced non-small cell lung cancer (NSCLC. The sensitivity of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs has been found to be associated with gene mutationss in the tyrosine kinase domain of RGFR. However, not all EGFR gene mutationss are sensitive to EGFR-TKIs. The review was conducted to study the research progress of EGFR mutations and the sensitivity to EGFR-TKIs and the mechanism of resistance of molecular target therapy in NSCLC.

  5. Research Progress of Epidermal Growth Factor Receptor and Molecular-Targeted Therapy in Treatment of Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Xiaoyou; Feng Jifeng

    2014-01-01

    Molecular target therapy has become a new approach in the treatment of advanced non-small cell lung cancer (NSCLC). The sensitivity of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been found to be associated with gene mutationss in the tyrosine kinase domain of RGFR. However, not all EGFR gene mutationss are sensitive to EGFR-TKIs. The review was conducted to study the research progress of EGFR mutations and the sensitivity to EGFR-TKIs and the mechanism of resistance of molecular target therapy in NSCLC.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. Analysis of complications and outcomes after pulmonary resection in patients aged 80 years or over with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Wen-bing LI

    2014-10-01

    Full Text Available Objective To explore the therapeutic effect and degree of safety in patients aged 80 years or over with nonsmall cell lung cancer undergoing radical resection. Methods A retrospective survey of 97 elder patients aged 80 years or over, in whom non-small cell lung cancer was pathologically confirmed after partial resection of the lung in Chinese PLA General Hospital from Jan. 2003 to Dec. 2012. The peri-operative features were evaluated, including gender, age, history of smoking, pulmonary function, surgical procedure, histopathologic type, pathologic stage, etc. The relation of the postoperative complications and mortality with the factors mentioned above was analyzed. Results Among all patients, the surgical procedure comprised 36 lobectomies, 31 segmentectomies, and 30 wedge resections. The histopathologic diagnosis showed there were adenocarcinoma in 51 patients, squamous cell carcinoma in 29, large cell carcinoma in 9, adenosquamous cell carcinoma in 6 and neuro-endocrine cell carcinomas in 2. The disease stage was determined as ⅠA in 55 cases, ⅠB in 33, ⅡA in 7, ⅢA in 2. The post-operative complications (POC occurred in 14 of 97 patients (14.4%, and the most common complication was cardiovascular complication (9 cases, followed by pulmonary complication (5 cases. Only two patients died to the complications, one of them was post-operative pneumonia and respiratory failure, and the other one was acute myocardial infarction. The survival rate of the 97 patients was 91.7%, 70.2% and 52.8% at 1, 3 and 5 years, respectively, and in the patients with stage I disease, the survival rate was 93.9%, 73.6% and 54.1%, respectively. Conclusion Advanced age is not a contraindication to radical pulmonary resection in patients over 80 years old suffering from early stage non-small cell lung cancer. DOI: 10.11855/j.issn.0577-7402.2014.10.13

  10. Fisetin induces apoptosis in human nonsmall lung cancer cells via a mitochondria-mediated pathway.

    Science.gov (United States)

    Kang, Kyoung Ah; Piao, Mei Jing; Hyun, Jin Won

    2015-03-01

    The present study investigated the apoptotic effects of fisetin, a phenolic compound, against the human nonsmall cell lung cancer cell line, NCI-H460. Fisetin showed dose-dependent cytotoxic activity against NCI-H460 cells, with 50% inhibition of cell viability occurring at a concentration of 75 μg/mL. Fisetin induced both the production of intracellular reactive oxygen species and apoptosis, as evidenced by apoptotic body formation, DNA fragmentation, an increase in the number of sub-G1 phase cells, and mitochondrial membrane depolarization. Moreover, fisetin significantly modulated the expression of apoptosis-associated proteins, resulting in reduced expression of B cell lymphoma-2, increased expression of Bcl-2-associated X protein, and activation of caspase-9 and caspase-3. In addition, pretreatment with a caspase inhibitor blocked fisetin-induced cell death.

  11. Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells.

    NARCIS (Netherlands)

    Broker, L.E.; Huisman, C.; Span, SW; Rodriguez, J.A.; Kruyt, F.A.E.; Giaccone, G.

    2004-01-01

    We have previously reported that the microtubule stabilizing agents (MSAs) paclitaxel, epothilone B and discodermolide induce caspase-independent cell death in non-small cell lung cancer (NSCLC) cells. Here we present two lines of evidence indicating a central role for the lysosomal protease catheps

  12. REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells.

    Science.gov (United States)

    Wang, Wenjie; Sheng, Wenjiong; Yu, Chenxiao; Cao, Jianping; Zhou, Jundong; Wu, Jinchang; Zhang, Huojun; Zhang, Shuyu

    2015-09-01

    Lung cancer remains the leading cause of cancer-related mortality worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer. Cisplatin plays a significant role in the management of human lung cancer. Translesion DNA synthesis (TLS) is involved in DNA damage repair. DNA polymerase ζ (Pol ζ) is able to mediate the DNA replication bypass of DNA damage, which is suggested to be involved in chemoresistance. REV3L is the catalytic subunit of Pol ζ. Due to its critical role in translesion DNA synthesis, whether REV3L modulates cisplatin response in NSCLC cells remains unknown. In this study, REV3L overexpression and silencing H1299 cell lines were established. The reports showed that cisplatin induced the expression of REV3L by recruiting Sp1 to its promoter. Similar results were obtained when the ability of the cells to express luciferase from a platinated plasmid was measured. Co-transfection of the reporter with the REV3L overexpression vector or REV3L plus REV7L significantly enhanced the reporter activity. Nuclear condensation and fragmentation of shRNA-REV3L H1299 cells were more pronounced than shRNA-NC H1299 cells after cisplatin exposure, indicating that REV3L overexpression abolished cisplatin-induced DNA damage. Moreover, a forced expression of REV3L conferred the resistance of H1299 cells to cisplatin, whereas the knockdown of REV3L sensitized cisplatin efficacy in H1299 cells. Taken together, we demonstrated that inhibition of REV3L sensitized lung cancer H1299 cells to cisplatin treatment. Thus, REV3L may be a novel target for the chemotherapy of NSCLC.

  13. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKCα double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of...

  14. Carboplatin plus VP-16 with simultaneous radiotherapy in the treatment of non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Imanaka, Kazufumi; Kodama, Akihisa; Okamoto, Yoshiaki; Izumiyama, Kazutaka; Sakaguchi, Toshiya; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1995-01-01

    Ten patients with non-small cell lung cancer were treated by concurrent chemoradiotherapy. The protocol consists of split course radiotherapy and simultaneous chemotherapy (carboplatin plus VP-16). All patients tolerated well this treatment with no life-threatening complications and treatment duration was shortened compared to that of sequential chemoradiotherapy. Response rate was 50% (CR: 1, PR: 4), median survival time was 12.8 months and 2-year survival rate was 20%. The major toxicity was leucopenia, with WHO grade 4 leucopenia in 3 patients and grade 3 in 3 patients. This protocol was considered to be tolerable and effective for the treatment of non-small cell lung cancer. (author).

  15. Proteasome-based mechanisms of intrinsic and acquired bortezomib resistance in non-small cell lung cancer

    NARCIS (Netherlands)

    de Wilt, Leonie H. A. M.; Jansen, Gerrit; Assaraf, Yehuda G.; van Meerloo, Johan; Cloos, Jacqueline; Schimmer, Aaron D.; Chan, Elena T.; Kirk, Christopher J.; Peters, Godefridus J.; Kruyt, Frank A. E.

    2012-01-01

    The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC). Here we studied the proteasome-based mechanisms underlying intrinsic and acquired bortezomib resistance in NSCLC cells. Var

  16. Non-small cell lung cancer cell survival crucially depends on functional insulin receptors.

    Science.gov (United States)

    Frisch, Carolin Maria; Zimmermann, Katrin; Zilleßen, Pia; Pfeifer, Alexander; Racké, Kurt; Mayer, Peter

    2015-08-01

    Insulin plays an important role as a growth factor and its contribution to tumor proliferation is intensely discussed. It acts via the cognate insulin receptor (IR) but can also activate the IGF1 receptor (IGF1R). Apart from increasing proliferation, insulin might have additional effects in lung cancer. Therefore, we investigated insulin action and effects of IR knockdown (KD) in three (NCI-H292, NCI-H226 and NCI-H460) independent non-small cell lung cancer (NSCLC) cell lines. All lung cancer lines studied were found to express IR, albeit with marked differences in the ratio of the two variants IR-A and IR-B. Insulin activated the classical signaling pathway with IR autophosphorylation and Akt phosphorylation. Moreover, activation of MAPK was observed in H292 cells, accompanied by enhanced proliferation. Lentiviral shRNA IR KD caused strong decrease in survival of all three lines, indicating that the effects of insulin in lung cancer go beyond enhancing proliferation. Unspecific effects were ruled out by employing further shRNAs and different insulin-responsive cells (human pre-adipocytes) for comparison. Caspase assays demonstrated that IR KD strongly induced apoptosis in these lung cancer cells, providing the physiological basis of the rapid cell loss. In search for the underlying mechanism, we analyzed alterations in the gene expression profile in response to IR KD. A strong induction of certain cytokines (e.g. IL20 and tumour necrosis factor) became obvious and it turned out that these cytokines trigger apoptosis in the NSCLC cells tested. This indicates a novel role of IR in tumor cell survival via suppression of pro-apoptotic cytokines.

  17. 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.

  18. Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application.

    Science.gov (United States)

    Yuan, Xun; Wu, Hua; Han, Na; Xu, Hanxiao; Chu, Qian; Yu, Shiying; Chen, Yuan; Wu, Kongming

    2014-12-05

    Through epithelial-mesenchymal transition (EMT), cancer cells acquire enhanced ability of migration and invasion, stem cell like characteristics and therapeutic resistance. Notch signaling regulates cell-cell connection, cell polarity and motility during organ development. Recent studies demonstrate that Notch signaling plays an important role in lung cancer initiation and cross-talks with several transcriptional factors to enhance EMT, contributing to the progression of non-small cell lung cancer (NSCLC). Correspondingly, blocking of Notch signaling inhibits NSCLC migration and tumor growth by reversing EMT. Clinical trials have showed promising effect in some cancer patients received treatment with Notch1 inhibitor. This review attempts to provide an overview of the Notch signal in NSCLC: its biological significance and therapeutic application.

  19. Identification of Serum Peptidome Signatures of Non-Small Cell Lung Cancer

    OpenAIRE

    Agnieszka Klupczynska; Agata Swiatly; Joanna Hajduk; Jan Matysiak; Wojciech Dyszkiewicz; Krystian Pawlak; Zenon J. Kokot

    2016-01-01

    Due to high mortality rates of lung cancer, there is a need for identification of new, clinically useful markers, which improve detection of this tumor in early stage of disease. In the current study, serum peptide profiling was evaluated as a diagnostic tool for non-small cell lung cancer patients. The combination of the ZipTip technology with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for the analysis of peptide pattern of cancer patients (n ...

  20. Pulmonary Artery Agenesis Associated With Emphysema and Multiple Invasive Non-Small Cell Lung Cancers.

    Science.gov (United States)

    Makdisi, George; Edell, Eric S; Maleszewski, Joseph J; Molina, Julian R; Deschamps, Claude

    2015-06-01

    Pulmonary artery (PA) agenesis in the absence of associated cardiac abnormalities is a rare congenital abnormality. It may remain undiagnosed until adulthood when patients present with respiratory symptoms such as hemoptysis, dyspnea, repeated respiratory infections, or pulmonary hypertension. Herein we present a case of a 50-year-old woman who was found to have multiple, morphologically distinct non-small cell lung cancers in association with agenesis of the PA. This instance represents the fourth reported case of such association in the English literature.

  1. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

  2. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    Class-III-beta-tubulin (TUBB3) expression may be a potential predictive factor for treatment with microtubule interfering cytotoxic drugs in non-small cell lung cancer (NSCLC). Potential changes in TUBB3 expression during chemotherapy may be of interest if future choice of chemotherapy...... is to be based on TUBB3 expression. If the biomarker expression changes during chemotherapy, biopsies before initiation of chemotherapy beyond first line may be needed if treatment decision is to be based on TUBB3 expression. Thus, the aim was to explore TUBB3 expression heterogeneity and changes during...

  3. [Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis].

    Science.gov (United States)

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.

  4. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Qi SONG

    2016-08-01

    Full Text Available Brain metastasis, a common complication of non-small cell lung cancer (NSCLC with an incidence rate of 30%-50%, significantly affects the patients’ quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work.

  5. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    OpenAIRE

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-01-01

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients’ quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approa...

  6. A Preliminary Analysis of Non-small Cell Lung Cancer Biomarkers in Serum

    Institute of Scientific and Technical Information of China (English)

    XUE-YUAN XIAO; YING TANG; XIU-PING WEI; DA-CHENG HE

    2003-01-01

    Objective To identify potential serum biomarkers that could be used to discriminate lungcancers from normal. Methods Proteomic spectra of twenty-eight serum samples from patientswith non-small cell lung cancer and twelve from normal individuals were generated by SELDI(Surfaced Enhanced Laser Desorption/Ionization) Mass Spectrometry. Anion-exchange columns wereused to fractionate the sera into 6 designated pH groups. Two different types of protein chip arrays,IMAC-Cu and WCX2, were employed. Samples were examined in PBSII Protein Chip Reader(Ciphergen Biosystem Inc) and the discriminatory profiling between cancer and normal samples wasanalyzed with Biomarker Pattern software. Results Five distinct potential lung cancer biomarkerswith higher sensitivity and specificity were found, with four common biomarkers in both IMAC-Cuand WCX2 chip; the remaining biomarker occurred only in WCX2 chip. Two biomarkers wereup-regulated while three biomarkers were down-regulated in the serum samples from patients withnon-small cell lung cancer. The sensitivities provided by the individual biomarkers were 75%-96.43%and specificities were 75%-100%. Conclusions The preliminary results suggest that serum is acapable resource for detecting specific non-small cell lung cancer biomarkers. SELDI massspectrometry is a useful tool for the detection and identification of new potential biomarker ofnon-small cell lung cancer in serum.

  7. Genomic profiling toward precision medicine in non-small cell lung cancer: getting beyond EGFR

    Directory of Open Access Journals (Sweden)

    Richer AL

    2015-02-01

    Full Text Available Amanda L Richer,1 Jacqueline M Friel,1 Vashti M Carson,2 Landon J Inge,1 Timothy G Whitsett2 1Norton Thoracic Institute, St Joseph’s Hospital and Medical Center, 2Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: Lung cancer remains the leading cause of cancer-related mortality worldwide. The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of non-small cell lung cancer (NSCLC. A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor (EGFR have been identified in NSCLC. While targeted therapeutic successes have been demonstrated in the therapeutic targeting of EGFR and ALK, the majority of NSCLC tumors do not harbor these genomic events. This review looks at the current treatment paradigms for lung adenocarcinomas and squamous cell carcinomas, examining genomic aberrations that dictate therapy selection, as well as novel therapeutic strategies for tumors harboring mutations in KRAS, TP53, and LKB1 which, to date, have been considered “undruggable”. A more thorough understanding of the molecular alterations that govern NSCLC tumorigenesis, aided by next-generation sequencing, will lead to targeted therapeutic options expected to dramatically reduce the high mortality rate observed in lung cancer. Keywords: non-small cell lung cancer, precision medicine, epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine kinase 11, tumor protein p53

  8. 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.

  9. 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

  10. Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Mei-Chuan Tang

    Full Text Available Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, are effective for non-small cell lung cancer (NSCLC patients with EGFR mutations. However, these patients eventually develop resistance to EGFR-TKI. The goal of the present study was to investigate the involvement of autophagy in gefitinib resistance. We developed gefitinib-resistant cells (PC-9/gef from PC-9 cells (containing exon 19 deletion EGFR after long-term exposure in gefitinib. PC-9/gef cells (B4 and E3 were 200-fold more resistant to gefitinib than PC-9/wt cells. Compared with PC-9/wt cells, both PC-9/gefB4 and PC-9/gefE3 cells demonstrated higher basal LC3-II levels which were inhibited by 3-methyladenine (3-MA, an autophagy inhibitor and potentiated by chloroquine (CQ, an inhibitor of autophagolysosomes formation, indicating elevated autophagy in PC-9/gef cells. 3-MA and CQ concentration-dependently inhibited cell survival of both PC-9wt and PC-9/gef cells, suggesting that autophagy may be pro-survival. Furthermore, gefitinib increased LC3-II levels and autolysosome formation in both PC-9/wt cells and PC-9/gef cells. In PC-9/wt cells, CQ potentiated the cytotoxicity by low gefitinib (3 nM. Moreover, CQ overcame the acquired gefitinib resistance in PC-9/gef cells by enhancing gefitinib-induced cytotoxicity, activation of caspase 3 and poly (ADP-ribose polymerase cleavage. Using an in vivo model xenografting with PC-9/wt and PC-9/gefB4 cells, oral administration of gefitinib (50 mg/kg completely inhibited the tumor growth of PC-9/wt but not PC-9/gefB4cells. Combination of CQ (75 mg/kg, i.p. and gefitinib was more effective than gefitinib alone in reducing the tumor growth of PC-9/gefB4. Our data suggest that inhibition of autophagy may be a therapeutic strategy to overcome acquired resistance of gefitinib in EGFR mutation NSCLC patients.

  11. Application of non-small cell lung cancer pleural effusion cell blocks in molecular pathological detection

    Institute of Scientific and Technical Information of China (English)

    Ying Zhang; Nan Jiang; Dongdong Qian; Xiangzhou Li; Yu Zhou; Jia Mei; Xiaohui Cao

    2014-01-01

    Objective:The tumor tissues used in molecular pathological detection were usual y obtained by surgery, which would cause trauma and may not be suitable for the terminal cancer patients. This paper evaluated the value of the non-smal celllung cancer (NSCLC) pleural ef usion cellblocks as tumor tissues replacement materials in the application of molecular pathological detection. Methods: Tumor cells were made into cellblocks through stratified centrifugal from 30 NSCLC pa-tients with the pleural ef usion. The immunohistochemistry, fluorescence in situ hybridization (FISH) and gene sequencing methods were employed in our experiments. Results:The tumor cells of cellblock section were rich and could keep part of histological structure. Immunohistochemistry staining could assist diagnosis and tumor parting. Epidermal growth factor receptor (EGFR) FISH-positive was found in 33.33%of the group, high polysomy in 6 cases, amplification in 4 cases. EGFR gene mutations were found in 8 cases of 30 samples, with an incidence of 26.67%, 6 cases were detected in the exon 19, and 2 cases were detected in the exon 21. Conclusion:The NSCLC pleural ef usion cellblocks are useful for the diagnosis and determining the primary source of tumor, instructed targeted therapy.

  12. Spotlight on pembrolizumab in non-small cell lung cancer: the evidence to date

    Directory of Open Access Journals (Sweden)

    Vachhani P

    2016-09-01

    Full Text Available Pankit Vachhani, Hongbin Chen Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA Abstract: Immunotherapy with immune checkpoint inhibitors has opened a new arena in cancer therapeutics. Pembrolizumab is a highly selective anti-programmed cell death protein 1 (PD-1 antibody that has shown efficacy, leading to survival benefit and durable responses, in some patients with non-small cell lung cancer (NSCLC. It has been approved by the US Food and Drug Administration for the treatment of patients with metastatic NSCLC, whose tumors express PD-1 ligand 1 (PD-L1, with disease progression on or after platinum-containing chemotherapy. Here, we briefly discuss the PD-1/PD-L1 pathway and pembrolizumab before delving into the clinical trials that have led to its just-mentioned approval in NSCLC and ongoing clinical trials. Finally, we discuss the use of biomarkers, primarily PD-L1, in the context of pembrolizumab and NSCLC. Keywords: pembrolizumab, KEYNOTE, non-small cell lung cancer 

  13. ABCC4 is required for cell proliferation and tumorigenesis in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhao X

    2014-02-01

    Full Text Available Xiaoting Zhao, Yinan Guo, Wentao Yue, Lina Zhang, Meng Gu, Yue Wang Department of Cellular and Molecular Biology, Beijing TB and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China Background: Multidrug resistance protein 4 (MRP4, also known as ATP-cassette binding protein 4 (ABCC4, is a member of the MRP/ABCC subfamily of ATP-binding cassette transporters, which are capable of pumping a wide variety of drugs out of the cell. However, little is known about the function of ABCC4 in the proliferation of lung cancer cells. Methods: ABCC4 mRNA and protein levels in lung cancer cell lines were measured by real-time polymerase chain reaction and Western blot, respectively. A lentivirus-mediated RNA interference technique was used to inhibit ABCC4 mRNA expression in A549 and 801D cells. The function of ABCC4 in cell growth was investigated by MTS and colony formation assays. The role of ABCC4 in cell cycle progression was evaluated by flow cytometry and Western blot analysis. ABCC4 mRNA levels in 30 pairs of tumors and corresponding matched adjacent normal tissues from non-small cell lung cancer patients were detected by real-time polymerase chain reaction. Results: ABCC4 was highly expressed in lung cancer cell lines. ABCC4 expression was markedly downregulated in A549 and 801D cells using the RNA interference technique. Suppression of ABCC4 expression inhibited cell growth. The percentage of cells in G1 phase was increased when ABCC4 expression was suppressed. Phosphorylation of retinoblastoma protein was weakened, originating in the downregulation of ABCC4. ABCC4 mRNA was highly expressed in lung cancer tissue and lung cancer cell lines. Conclusion: ABCC4 may play an important role in the control of A549 and 801D cell growth. ABCC4 is a potential target for lung cancer therapy. Keywords: ABCC4, cell proliferation, lung cancer, cell cycle

  14. 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.

  15. Enhancement of radiosensitivity by CpG-oligodeoxyribonucleotide-7909 in human non-small cell lung cancer A549 cells.

    Science.gov (United States)

    Zha, Lin; Qiao, Tiankui; Yuan, Sujuan; Lei, Linjie

    2010-04-01

    CpG-oligodeoxyribonucleotides (CpG-ODNs), which induce signaling through the toll-like receptor 9, are currently under investigation as immunity stimulators against cancer. It has recently been suggested that CpG-ODNs may also enhance sensitivity to traditional therapies including chemotherapy in certain cancer-cell lines. The purpose of this study was to define the activity of CpG-ODN7909 in increasing radiosensitivity of the human non-small cell lung cancer cell line A549 in vitro. First, a dose- and time-dependent inhibitory effect on cell viability was observed after A549 cells were treated with different concentrations of CpG-ODN7909 (5, 10, 30, and 60 microg/mL). Second, decreased cell clonogenic survival, enhanced cell apoptotic index, accumulated percentage of cells in the G2/M phase, and increased tumor necrosis factor (TNF)-alpha secretion were found after combined treatments with 10 microg/mL of CpG-ODN7909 and radiation compared to either treatment alone (p CpG-ODN7909 can increase the radiosensitivity of human non-small cell lung cancer A549 cells, which may be associated with reduced cell clonogenic survival, enhanced apoptosis, prolonged cell-cycle arrest in G2/M, and stimulation of TNF-alpha secretion.

  16. Signatures of Drug Sensitivity in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hua C. Gong

    2011-01-01

    Full Text Available We profiled receptor tyrosine kinase pathway activation and key gene mutations in eight human lung tumor cell lines and 50 human lung tumor tissue samples to define molecular pathways. A panel of eight kinase inhibitors was used to determine whether blocking pathway activation affected the tumor cell growth. The HER1 pathway in HER1 mutant cell lines HCC827 and H1975 were found to be highly activated and sensitive to HER1 inhibition. H1993 is a c-MET amplified cell line showing c-MET and HER1 pathway activation and responsiveness to c-MET inhibitor treatment. IGF-1R pathway activated H358 and A549 cells are sensitive to IGF-1R inhibition. The downstream PI3K inhibitor, BEZ-235, effectively inhibited tumor cell growth in most of the cell lines tested, except the H1993 and H1650 cells, while the MEK inhibitor PD-325901 was effective in blocking the growth of KRAS mutated cell line H1734 but not H358, A549 and H460. Hierarchical clustering of primary tumor samples with the corresponding tumor cell lines based on their pathway signatures revealed similar profiles for HER1, c-MET and IGF-1R pathway activation and predict potential treatment options for the primary tumors based on the tumor cell lines response to the panel of kinase inhibitors.

  17. Deep sequencing of the TP53 gene reveals a potential risk allele for non-small cell lung cancer and supports the negative prognostic value of TP53 variants.

    Science.gov (United States)

    Deben, Christophe; Van den Bossche, Jolien; Van Der Steen, Nele; Lardon, Filip; Wouters, An; de Beeck, Ken Op; Hermans, Christophe; Jacobs, Julie; Peeters, Marc; Van Camp, Guy; Rolfo, Christian; Deschoolmeester, Vanessa; Pauwels, Patrick

    2017-02-01

    The TP53 gene remains the most frequently altered gene in human cancer, of which variants are associated with cancer risk, therapy resistance, and poor prognosis in several tumor types. To determine the true prognostic value of TP53 variants in non-small cell lung cancer, this study conducted further research, particularly focusing on subtype and tumor stage. Therefore, we determined the TP53 status of 97 non-small cell lung cancer adenocarcinoma patients using next generation deep sequencing technology and defined the prognostic value of frequently occurring single nucleotide polymorphisms and mutations in the TP53 gene. Inactivating TP53 mutations acted as a predictor for both worse overall and progression-free survival in stage II-IV patients and patients treated with DNA-damaging (neo)adjuvant therapy. In stage I tumors, the Pro-allele of the TP53 R72P polymorphism acted as a predictor for worse overall survival. In addition, we detected the rare R213R (rs1800372, minor allele frequency: 0.0054) polymorphism in 7.2% of the patients and are the first to show the significant association with TP53 mutations in non-small cell lung cancer adenocarcinoma patients (p = 0.003). In conclusion, Our findings show an important role for TP53 variants as negative predictors for the outcome of non-small cell lung cancer adenocarcinoma patients, especially for TP53 inactivating mutations in advanced stage tumors treated with DNA-damaging agents, and provide the first evidence of the R213R G-allele as possible risk factor for non-small cell lung cancer.

  18. 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

  19. 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

  20. 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

  1. 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)

  2. 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

  3. 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.

  4. Tailoring treatment of nonsmall cell lung cancer by tissue type: role of pemetrexed

    Directory of Open Access Journals (Sweden)

    Steven F Powell

    2009-06-01

    Full Text Available Steven F Powell1, Arkadiusz Z Dudek21Department of Medicine, University of Minnesota, Minneapolis, MN, USA; 2Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USAAbstract: Pemetrexed (ALIMTA, LY231514, MTA is a novel multitargeted antifolate that is currently approved for the treatment of metastatic nonsmall cell lung cancer (NSCLC. Recent evidence reveals that the drug’s efficacy is limited to nonsquamous lung cancer histology. As we further understand the drug’s mechanisms of action, new genomic and proteomic evidence is shedding light on why some patients respond while others do not. The first goal of this review is to briefly review pemetrexed’s mechanism of action, resistance patterns, toxicity profile, and pharmacokinetics. We will also review the clinical trials that led to its use in NSCLC, with special attention to data showing that pemetrexed has greater efficacy in nonsquamous histologies of NSCLC. Furthermore, we will discuss the hypotheses for the genomic and proteomic basis for this variation in efficacy. Finally, we will report the future directions for pemetrexed as a personalized agent for nonsquamous NSCLC.Keywords: nonsmall cell lung cancer, pemetrexed, antifoliate

  5. 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.

  6. Radiosensitization of non-small cell lung cancer by kaempferol.

    Science.gov (United States)

    Kuo, Wei-Ting; Tsai, Yuan-Chung; Wu, His-Chin; Ho, Yung-Jen; Chen, Yueh-Sheng; Yao, Chen-Han; Yao, Chun-Hsu

    2015-11-01

    The aim of the present study was to determine whether kaempferol has a radiosensitization potential for lung cancer in vitro and in vivo. The in vitro radio-sensitization activity of kaempferol was elucidated in A-549 lung cancer cells by using an MTT (3-(4 5-dimethylthiazol-2-yl)-25-diphenyl-tetrazolium bromide) assay, cell cycle analysis and clonogenic assay. The in vivo activity was evaluated in the BALB/c nude mouse xenograft model of A-549 cells by hematoxylin and eosin staining and immunohistochemistry, and the tumor volume was recorded. Protein levels of the apoptotic pathway were detected by western blot analysis. Treatment with kaempferol inhibited the growth of A-549 cells through activation of apoptotic pathway. However, the same doses did not affect HFL1 normal lung cell growth. Kaempferol induced G2/M cell cycle arrest and the enhancement of radiation-induced death and clonogenic survival inhibition. The in vivo data showed that kaempferol increased tumor cell apoptosis and killing of radiation. In conclusion, the findings demonstrated that kaempferol increased tumor cell killing by radiation in vitro and in vivo through inhibition of the AKT/PI3K and ERK pathways and activation of the mitochondria apoptosis pathway. The results of the present study provided solid evidence that kaempferol is a safe and potential radiosensitizer.

  7. The effects on surgery and preoperative patients with non-small cell lung cancer by preoperative bronchial artery infusion chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Shuhong Tang; Jilai Bian; Mingwu Li

    2008-01-01

    Objective: To study the efficiency, safety and feasibility of preoperative bronchial artery infusion (BAI) chemotherapy on operation in patients with locally advanced (stage Ⅲ) non-small cell lung cancer (NSCLC).Methods: 92 cases with locally advanced NSCLC patients were randomly divided into two groups: (1) BAI chemotherapy group: 39 cases were received BAI chemotherapy for 2 courses and followed surgery; (2) surgery alone group: 51 cases were treated by operation alone.The complete resection rate and preoperative complications were compared between these two groups.Results: In BAI chemotherapy group, the rate of clinical efficiency was 68.3% with slight toxicity.In BAI chemotherapy group the surgery complete resection rate was 89.7%, which was significantly higher than that in surgery alone group (72.5%, P<0.05).No significant differences of blood loss, operative complications and mortality were observed between these two groups.Conclusion: BAI neoadjuvant chemotherapy was safe and effective, which can increase the complete resection rate of the tumor and did not increase the operative complications and mortality.

  8. The importance of pre-treatment haemoglobin level in inoperable non-small cell lung carcinoma treated with radical radiotherapy

    NARCIS (Netherlands)

    Langendijk, H; de Jong, J; Wanders, R; Lambin, P; Slotman, B

    2003-01-01

    Background and purpose: The purpose of this study was to evaluate the prognostic significance of the pre-treatment haemoglobin level among patients with inoperable non-small cell lung carcinorna (NSCLC) treated with definitive radiotherapy with regard to loco-regional tumour control (LC) and overall

  9. Chronic Obstructive Pulmonary Disease Is Not Associated with KRAS Mutations in Non-Small Cell Lung Cancer

    NARCIS (Netherlands)

    Saber, Ali; Wekken, van der Anthonie; Kerner, Gerald S M A; van den Berge, Maarten; Timens, Wim; Schuuring, Ed; Ter Elst, Arja; van den Berg, Anke; Hiltermann, T Jeroen N; Groen, Harry J M

    2016-01-01

    Mutations in epithelial growth factor receptor (EGFR), as well as in the EGFR downstream target KRAS are frequently observed in non-small cell lung cancer (NSCLC). Chronic obstructive pulmonary disease (COPD), an independent risk factor for developing NSCLC, is associated with an increased activatio

  10. Chemotherapy response evaluation with 18F-FDG PET in patients with non-small cell lung cancer

    NARCIS (Netherlands)

    de Geus-Oei, Lioe-Fee; van der Heijden, Henricus F. M.; Visser, Eric P.; Hermsen, Rick; van Hoorn, Bas A.; Timmer-Bonte, Johanna N. H.; Willemsen, Antoon T.; Pruim, Jan; Corstens, Frans H. M.; Krabbe, Paul F. M.; Oyen, Wim J. G.

    2007-01-01

    The aim of this prospective study was to evaluate the value of F-18-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism. Methods: In 51 pat

  11. The prognostic value of positron emission tomography in non-small cell lung cancer : Analysis of 266 cases

    NARCIS (Netherlands)

    Kramer, H.; Post, W.J.; Pruim, J.; Groen, H.J.M.

    2006-01-01

    Positron emission tomography (PET) is more accurate than computed tomography (CT) in the staging of non-small cell lung cancer (NSCLC). We analyzed the prognostic value of PET for survival in NSCLC patients. Methods: Consecutive patients with proven NSCLC with PET for staging were selected. Staging

  12. Long-Term Excess Mortality for Survivors of Non-small Cell Lung Cancer in the Netherlands

    NARCIS (Netherlands)

    Janssen-Heijnen, Maryska L.; van Steenbergen, Liza N.; Steyerberg, Ewout; Visser, Otto; De Ruysscher, Dirk K.; Groen, Harry J.

    2012-01-01

    Introduction: Most patients diagnosed with non-small cell lung cancer (NSCLC) die within the first few years after diagnosis. However, only little is known about those who have survived these first years. We aimed to study conditional 5-year relative survival rates for NSCLC patients during long-ter

  13. Iron deficiency anemia as initial presentation of a non-small cell lung carcinoma: A case report

    NARCIS (Netherlands)

    P.V.M. Linsen (Philip V.M.); V.M.J. Linsen (Victor M.J.); G. Buunk (Gerba); D.E. Arnold (Dorothee E.); J.G.J.V. Aerts (Joachim)

    2015-01-01

    textabstractDuodenal metastases secondary to lung cancer are very rare and most of the time asymptomatic. When symptomatic they usually present with bowel obstruction or perforation. We here describe the case of a 68 year-old man with a solitary metastasis in the duodenum from a non-small cell lung

  14. Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer

    DEFF Research Database (Denmark)

    Bernchou, Uffe; Christiansen, Rasmus Lübeck; Asmussen, Jon Thor

    2017-01-01

    BACKGROUND AND PURPOSE: The present study investigates the extent and appearance of radiologic injury in the lung after radiotherapy for non-small cell lung cancer (NSCLC) patients and correlates radiologic response with clinical and dosimetric factors. METHODS AND MATERIALS: Eligible follow-up C...

  15. Comparison of survival of chronic obstructive pulmonary disease patients with or without a localized non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Gerner Hansen, Niels-Christian; Schytte, Tine

    2016-01-01

    OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are often co-existing diseases with poor prognosis. The aim of this study was to compare survival in COPD patients with localized NSCLC treated with stereotactic body radiotherapy (NSCLC group) with COPD...

  16. Targeted therapies in development for non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Thanyanan Reungwetwattana

    2013-01-01

    Full Text Available The iterative discovery in various malignancies during the past decades that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by "druggable" protein kinases has led to a revolutionary change in drug development. In non-small cell lung cancer (NSCLC, the ErbB family of receptors (e.g., EGFR [epidermal growth factor receptor], HER2 [human epidermal growth factor receptor 2], RAS (rat sarcoma gene, BRAF (v-raf murine sarcoma viral oncogene homolog B1, MAPK (mitogen-activated protein kinase c-MET (c-mesenchymal-epithelial transition, FGFR (fibroblast growth factor receptor, DDR2 (discoidin domain receptor 2, PIK3CA (phosphatidylinositol-4,5-bisphosphate3-kinase, catalytic subunit alpha, PTEN (phosphatase and tensin homolog, AKT (protein kinase B, ALK (anaplastic lym phoma kinase, RET (rearranged during transfection, ROS1 (reactive oxygen species 1 and EPH (erythropoietin-producing hepatoma are key targets of various agents currently in clinical development. These oncogenic targets exert their selective growth advantage through various intercommunicating pathways, such as through RAS/RAF/MEK, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin and SRC-signal transduction and transcription signaling. The recent clinical studies, EGFR tyrosine kinase inhibitors and crizotinib were considered as strongly effective targeted therapies in metastatic NSCLC. Currently, five molecular targeted agents were approved for treatment of advanced NSCLC: Gefitinib, erlotinib and afatinib for positive EGFR mutation, crizotinib for positive echinoderm microtubule-associated protein-like 4 (EML4-ALK translocation and bevacizumab. Moreover, oncogenic mutant proteins are subject to regulation by protein trafficking pathways, specifically through the heat shock protein 90 system. Drug combinations affecting various nodes in these signaling and intracellular processes are predicted and demonstrated to be synergistic and

  17. Sec62 bridges the gap from 3q amplification to molecular cell biology in non-small cell lung cancer.

    Science.gov (United States)

    Linxweiler, Maximilian; Linxweiler, Johannes; Barth, Monika; Benedix, Julia; Jung, Volker; Kim, Yoo-Jin; Bohle, Rainer M; Zimmermann, Richard; Greiner, Markus

    2012-02-01

    The molecular carcinogenesis of lung cancer has yet to be clearly elucidated. We investigated the possible oncogenic function of SEC62 in lung cancer, which was predicted based on our previous findings that lung and thyroid cancer tissue samples exhibited increased Sec62 protein levels. The SEC62 gene locus is at 3q26.2, and 3q amplification is reportedly the most common genomic alteration in non-small cell lung cancer. We analyzed SEC62 mRNA and protein levels in tissue samples from lung cancer patients by real-time quantitative PCR, Western blot, and IHC and found significantly increased SEC62 mRNA and protein levels in tumors compared with tumor-free tissue samples from the same patients. Correlation analyses revealed significantly higher Sec62 levels in tumors with lymph node metastases compared with nonmetastatic tumors, as well as in poorly compared with moderately differentiated tumors. On the basis of these promising results, we examined the role of Sec62 in cancer cell biology in vitro. Cell migration assays with lung and thyroid cancer cells showed distinct stimulation of migration in SEC62-overexpressing cells and inhibition of migration in Sec62-depleted cells. Moreover, we found that SEC62 silencing sensitized the cells to thapsigargin-induced endoplasmic reticulum stress. Thus, our results indicate that SEC62 represents a potential candidate oncogene in the amplified 3q region in cases of non-small cell lung cancer and harbors various functions in cancer cell biology.

  18. [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

  19. Role of Metallothionein1H in Cisplatin Resistance of Non-Small Cell Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Xin-fang Hou; Qing-xia Fan; Liu-xing Wang; Shi-xin Lu

    2009-01-01

    Objective: Despite platinum-based adjuvant chemotherapy has improved greatly patients' outcomes, drug resistance poses a major impediment to the successful use of such an effective agent. Metallothioneins(MTs) are known to play putative roles in cancer cell proliferation, apoptosis, differentiation, drug resistance and prognosis. The present studiy was to investigte the role of metallethioein1H(MT1H) in cisplatin resistance of human non-small cell lung cancer(NSCLC) cell lines in vitro or its possible molecular mechanisms. Methods: MT1H mRNA expression in A549 and A549/DDP cells was detected by RT-PCR. A recombinant eukaryotic expression plasmid pcDNA3.1(-)-MT1H was constructed and transfected into A549 cells which express no MT1H. MT1H siRNA was transfected into A549/DDP cells which express MT1H highly. MT1H expression was detected by RT-PCR and Immunoblot. The chemosensitivity to cisplatin was assessed by MTT assay. Apoptosis rate was determined by Tunel and FCM. Bcl-2 and Bax were determined by immunohistochemistry. Results: MT1H mRNA was expressed in A549/DDP but not in A549. After transfection of MT1H, MT1H expression was enhanced and the chemosensitivity to cisplatin was decreased in A549 cells. Inversely, after transfection of MT1H siRNA, MT1H expression was decreased and the chemosensitivity to cisplatin was increased in A549/DDP. The apoptosis rate induced by cisplatin was increased and Bcl-2 was down-regulated but Bax showed little change in A549/DDP cells interferred with MT1H siRNA. Conclusion: MT1H overexpression can promote drug resistance in A549 cells . Down-regulation of MT1H interfered with siRNA can effectively reverses the drug resistance in A549/DDP cells by down-regulating the expression of Bcl-2 and increasing cisplatin induced apoptosis. SiRNA targeting MT1H combined with chemotherapy may be a very promising strategy for treatment of lung cancer.

  20. Expression of Bim, Noxa, and Puma in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Sakakibara-Konishi Jun

    2012-07-01

    Full Text Available Abstract Background The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC. Methods A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Bim, Noxa, and Puma expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes were analyzed. Results Immunohistochemical reactivity for Bim, Noxa, and Puma was detected in the cytoplasm of the tumor cells. Bim expression was associated with several clinicopathological factors, including sex (p  Conclusions The current analyses demonstrated that Bim expression in the NSCLCs was associated with both squamous cell carcinoma histology and tumor proliferation.

  1. Subtyping of nonsmall cell lung cancer on cytology specimens: Reproducibility of cytopathologic diagnoses on sparse material

    DEFF Research Database (Denmark)

    Haukali, O. S.; Henrik, H.; Olsen, Karen Ege;

    2014-01-01

    Cytologic examination of fine-needle aspiration (material is increasingly used in diagnosing lung cancer. High interobserver agreement in distinguishing small-cell lung cancer from nonsmall-cell lung cancer (NSCLC) on cytologic material has been demonstrated. Because of new treatment......-modalities, subclassification of NSCLC into squamous cell carcinoma (SQC) and non-SQC has clinical impact. Subclassification based on morphology alone may be difficult, but applying immunohistochemistry (IHC) to clot-material has proved helpful. When insufficient material is available to make a clot from the aspirate......-Grunwald-Giemsa (MGG) stained smears and CS with IHC on material from 79 patients suspected of having lung cancer was included. The material was circulated twice to four pathologists. The diagnoses were categorized in five groups: SQC, adenocarcinoma of the lung, non-SQC, benign lesion and other forms of malignancy...

  2. miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Gang Chen

    Full Text Available Aberrant expression of microRNA-146a (miR-146a has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to various aspects of the malignant phenotype of human NSCLCs. In functional experiments, miR-146a suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292. miR-146a also inhibited the migratory capacity of these NSCLC cells. On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib and a monoclonal antibody (cetuximab. These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation, but were less potent compared to the effects of siRNA targeting of EGFR. Our results suggest that these effects of miR-146a are due to its targeting of EGFR and NF-κB signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE lung cancer samples, that low expression of miR-146a was correlated with advanced clinical TNM stages and distant metastasis in NSCLC (P<0.05. The patients with high miR-146a expression in their tumors showed longer progression-free survival (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients, P<0.05. miR-146a is therefore a strong candidate prognostic biomarker in NSCLC. Thus inducing miR-146a might be a therapeutic strategy for NSCLC.

  3. 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

  4. Double primary non-small cell lung cancer with synchronous small cell lung cancer N2 nodes: a case report

    OpenAIRE

    Gogakos, Apostolos S; Paliouras, Dimitrios; Rallis, Thomas; Chatzinikolaou, Fotios; Xirou, Persefoni; Tsirgogianni, Katerina; Tsavlis,Drosos; Sachpekidis,Nikos; Tsakiridis, Kosmas; Mpakas, Andreas; Zarogoulidis, Konstantinos; Zissimopoulos, Athanasios; Zarogoulidis, Paul; Barbetakis, Nikolaos

    2015-01-01

    Synchronous multiple primary lung cancer (SMPLC) is rare and very hard to distinguish from metastatic disease. Recent studies indicate the presence of this entity in the lung, with no mention to the involvement of the mediastinum. An extremely rare case of a 68-year-old male with double primary non-small cell lung cancer (NSCLC) in the left upper lobe and N2 positive nodes for small cell lung cancer (SCLC) is presented. Modern diagnostic criteria as well as aggressive curative strategies are ...

  5. Double primary non-small cell lung cancer with synchronous small cell lung cancer N2 nodes: a case report.

    Science.gov (United States)

    Gogakos, Apostolos S; Paliouras, Dimitrios; Rallis, Thomas; Chatzinikolaou, Fotios; Xirou, Persefoni; Tsirgogianni, Katerina; Tsavlis, Drosos; Sachpekidis, Nikos; Tsakiridis, Kosmas; Mpakas, Andreas; Zarogoulidis, Konstantinos; Zissimopoulos, Athanasios; Zarogoulidis, Paul; Barbetakis, Nikolaos

    2015-07-01

    Synchronous multiple primary lung cancer (SMPLC) is rare and very hard to distinguish from metastatic disease. Recent studies indicate the presence of this entity in the lung, with no mention to the involvement of the mediastinum. An extremely rare case of a 68-year-old male with double primary non-small cell lung cancer (NSCLC) in the left upper lobe and N2 positive nodes for small cell lung cancer (SCLC) is presented. Modern diagnostic criteria as well as aggressive curative strategies are encouraged, in order to achieve better survival rates for such patients.

  6. 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.

    Directory of Open Access Journals (Sweden)

    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.

  7. Nonsmall Cell Lung Cancer Therapy: Insight into Multitargeted Small-Molecule Growth Factor Receptor Inhibitors

    Directory of Open Access Journals (Sweden)

    Mridul Roy

    2013-01-01

    Full Text Available To date, lung cancer is the leading cause of cancer-related death worldwide, among which nonsmall cell lung cancer (NSCLC comprises about 85%. Taking into account the side effects of surgery, radiation, platinum-based doublet chemotherapy, and the growth self-sufficiency characteristic of cancer cells, drugs have been discovered toward growth factor receptor (GFR to treat NSCLC. As expected, these drugs provide a greater benefit. To increase the efficacy of such growth factor receptor tyrosine kinase inhibitors (RTKIs, coinhibition of GFR signaling pathways and combination of inhibitors along with radiation or chemotherapy have drew intense insight. Although clinical trials about single-agent RTKIs or their combination strategies suggest their increase potency against cancer, they are not beyond adverse effects, and sometimes the effects are more deadly than chemotherapy. Nevertheless the hope for RTKIs may be proved true by further researches and digging deep into cancer therapeutics.

  8. Biochip-Based Detection of KRAS Mutation in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Barbara Ziegler

    2011-11-01

    Full Text Available This study is aimed at evaluating the potential of a biochip assay to sensitively detect KRAS mutation in DNA from non-small cell lung cancer (NSCLC tissue samples. The assay covers 10 mutations in codons 12 and 13 of the KRAS gene, and is based on mutant-enriched PCR followed by reverse-hybridization of biotinylated amplification products to an array of sequence-specific probes immobilized on the tip of a rectangular plastic stick (biochip. Biochip hybridization identified 17 (21% samples to carry a KRAS mutation of which 16 (33% were adenocarcinomas and 1 (3% was a squamous cell carcinoma. All mutations were confirmed by DNA sequencing. Using 10 ng of starting DNA, the biochip assay demonstrated a detection limit of 1% mutant sequence in a background of wild-type DNA. Our results suggest that the biochip assay is a sensitive alternative to protocols currently in use for KRAS mutation testing on limited quantity samples.

  9. BLOOD TELOMERASE ACTIVITY AND ITS CORRELATIVITY WITH NON-SMALL CELL LUNG CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    胡坚; 李任远; 孙骊; 倪一鸣

    2004-01-01

    Objective: To study the correlativity between blood telomerase activity and Non-small cell lung carcinoma (NSCLC) through relative quantitative analysis of telomerase activity. Methods: Thirty-eight NSCLC and 25 inpatients with benign lung disease were selected. Telomerase repeat amplification protocol was adopted. PCR products were assayed with ELISA. Results: (a) Blood telomerase activity during operation was higher than that before or after operation (P0.05). (c) Blood telomerase activity of adenocarcinoma during and after operation was higher than that before operation (P0.05). Conclusion: The qualitative assay of blood telomerase activity can be adopted as an assistant index for diagnosis of NSCLC. Postoperative blood telomerase activity of adenocarcinoma is higher than that of squamous carcinoma. It may be an evidence for the likelihood of adenocarcinoma to metastase through blood. Blood telomerase activity increases significantly during operation, suggesting that operation may cause more cancer cells entering into circulation.

  10. Oligometastatic Disease at Presentation or Recurrence for Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Daniel R. Gomez

    2012-01-01

    Full Text Available Oligometastatic Non-Small Cell Lung Cancer (NSCLC presents a unique opportunity for potential curative therapy. Improved cancer staging using PET/CT, MRI, and future cellular and molecular staging with circulating tumor cells and/or molecular markers will identify more patients with truly oligometastasis disease that will benefit from definitive local treatment. Recent development of noninvasive local ablative therapy such as stereotactic radiotherapy makes it possible to eradicate multiple local diseases with minimal side effect. Novel systemic therapy may also control systemic spread and therefore make it possible to improve survival by eliminating local diseases. More research, particularly prospective studies, is ideally randomized studies are needed to validate the concept of oligometastasis.

  11. PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jerfiz D. Constanzo

    2016-05-01

    Full Text Available The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation.

  12. 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

    Institute of Scientific and Technical Information of China (English)

    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

  13. Liquid Biopsy in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Molina-Vila, Miguel A.; Mayo-de-las-Casas, Clara; Giménez-Capitán, Ana; Jordana-Ariza, Núria; Garzón, Mónica; Balada, Ariadna; Villatoro, Sergi; Teixidó, Cristina; García-Peláez, Beatriz; Aguado, Cristina; Catalán, María José; Campos, Raquel; Pérez-Rosado, Ana; Bertran-Alamillo, Jordi; Martínez-Bueno, Alejandro; Gil, María-de-los-Llanos; González-Cao, María; González, Xavier; Morales-Espinosa, Daniela; Viteri, Santiago; Karachaliou, Niki; Rosell, Rafael

    2016-01-01

    Liquid biopsy analyses are already incorporated in the routine clinical practice in many hospitals and oncology departments worldwide, improving the selection of treatments and monitoring of lung cancer patients. Although they have not yet reached its full potential, liquid biopsy-based tests will soon be as widespread as “standard” biopsies and imaging techniques, offering invaluable diagnostic, prognostic, and predictive information. This review summarizes the techniques available for the isolation and analysis of circulating free DNA and RNA, exosomes, tumor-educated platelets, and circulating tumor cells from the blood of cancer patients, presents the methodological challenges associated with each of these materials, and discusses the clinical applications of liquid biopsy testing in lung cancer. PMID:28066769

  14. Increasing the accuracy of 18F-FDG PET/CT interpretation of "mildly positive" mediastinal nodes in the staging of non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Moloney, F

    2014-05-01

    The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC).

  15. Relationship between estrogen receptor α and β expression and clinicopathological characteristics in elderly patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李琳

    2013-01-01

    Objective To evaluate estrogen receptor(ER)α and β expressions in elderly patients with non-small cell lung cancer(NSCLC) in China and their relationship with clinical and pathological characteristics

  16. EZH2-mediated Puma gene repression regulates non-small cell lung cancer cell proliferation and cisplatin-induced apoptosis.

    Science.gov (United States)

    Liu, Haidan; Li, Wei; Yu, Xinfang; Gao, Feng; Duan, Zhi; Ma, Xiaolong; Tan, Shiming; Yuan, Yunchang; Liu, Lijun; Wang, Jian; Zhou, Xinmin; Yang, Yifeng

    2016-08-30

    Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain the silenced state of genes. EZH2 is the catalytic core and one of the most important components of the polycomb repressive complex 2 (PRC2). In non-small cell lung cancer (NSCLC) cells and primary lung tumors, we found that PRC2 components, including EZH2, are overexpressed. High levels of EZH2 protein were associated with worse overall survival rate in NSCLC patients. RNA interference mediated attenuation of EZH2 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model. Unexpectedly, we discovered that, in the suppression of EZH2, p53 upregulated modulator of apoptosis (PUMA) expression was concomitantly induced. This is achieved through EZH2 directly binds to the Puma promoter thus epigenetic repression of PUMA expression. Furthermore, cisplatin-induced apoptosis of EZH2-knocking down NSCLC cells was elevated as a consequence of increased PUMA expression. Our work reveals a novel epigenetic regulatory mechanism controlling PUMA expression and suggests that EZH2 offers a candidate molecular target for NSCLC therapy and EZH2-regulated PUMA induction would synergistically increase the sensitivity to platinum agents in non-small cell lung cancers.

  17. Overexpression of Inhibitor of Growth 4 Enhances Radiosensitivity in Non-Small Cell Lung Cancer Cell Line SPC-A1.

    Science.gov (United States)

    Pan, Xuan; Wang, Rui; Bian, Haibo; De, Wei; Zhang, Ping; Wei, Chenchen; Wang, Zhaoxia

    2016-07-04

    Inhibitor of growth 4 is a member of the inhibitor of growth family proteins, which is involved in cell apoptosis, migration, invasion, and cell cycle progress. In this study, we investigated the inhibitor of growth 4 level in non-small cell lung cancer tissues and explored the antitumor activity of inhibitor of growth 4 in vitro and in vivo using non-small cell lung cancer cell line SPC-A1 and its underlying molecular mechanisms. We also explored its role on the radiosensitivity in SPC-A1 cells. The level of inhibitor of growth 4 protein was significantly decreased in 28 cases of non-small cell lung cancer tissues in comparison with corresponding noncancerous lung epithelial tissues. Upregulation of inhibitor of growth 4 by plasmid pcDNA3.1-ING4 delivery could suppress proliferation and increase apoptosis of SPC-A1 cells both in vitro and in vivo Additionally, we found that overexpression of inhibitor of growth 4 in SPC-A1 cell line could lead to a higher Bcl-2/Bax ratio, which might be an important factor in the apoptosis regulation. Furthermore, overexpression of inhibitor of growth 4 enhanced the radiosensitivity of SPC-A1 cells to irradiation. Inhibitor of growth 4 upregulation plus radiotherapy induced synergistic tumor suppression in SPC-A1 xenografts implanted in athymic nude mice. Thus, the restoration of inhibitor of growth 4 function might provide a potential strategy for non-small cell lung cancer radiosensitization.

  18. EM011 activates a survivin-dependent apoptotic program in human non-small cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Yates Clayton

    2009-10-01

    Full Text Available Abstract Background Lung cancer remains a leading cause of cancer death among both men and women in the United States. Treatment modalities available for this malignancy are inadequate and thus new drugs with improved pharmacological profiles and superior therapeutic indices are being continually explored. Noscapinoids constitute an emerging class of anticancer agents that bind tubulin but do not significantly alter the monomer/polymer ratio of tubulin. EM011, a rationally-designed member of this class of non-toxic agents, is more potent than the lead molecule, noscapine. Results Here we report that EM011 inhibited proliferation of a comprehensive panel of lung cancer cells with IC50's ranging from 4-50 μM. In A549 human non-small cell lung cancer cells, the antiproliferative activity was mediated through blockage of cell-cycle progression by induction of a transient but robust mitotic arrest accompanied by activation of the spindle assembly checkpoint. The mitotically-arrested A549 cells then override the activated mitotic checkpoint and aberrantly exit mitosis without cytokinesis resulting in pseudo G1-like multinucleated cells that either succumb directly to apoptosis or continue another round of the cell-cycle. The accumulated enormous DNA perhaps acts as genotoxic stress to trigger cell death. EM011-induced apoptotic cell death in A549 cells was associated with a decrease of the Bcl2/BAX ratio, activation of caspase-3 and cleavage of PARP. Furthermore, EM011 induced downregulation of survivin expression over time of treatment. Abrogation of survivin led to an increase of cell death whereas, overexpression caused decreased apoptosis. Conclusion These in vitro data suggest that EM011 mediates antiproliferative and proapoptotic activity in non-small cell A549 lung cancer cells by impeding cell-cycle progression and attenuating antiapoptotic signaling circuitries (viz. Bcl2, survivin. The study provides evidence for the potential usefulness of

  19. 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

  20. 新辅助化疗对局部晚期非小细胞肺癌肿瘤标记物和淋巴细胞亚群的影响%Effect of neoadjuvant chemotherapy on locally advanced non-small cell lung cancer tumor markers and lymphocyte subsets

    Institute of Scientific and Technical Information of China (English)

    王纯; 卢宏达

    2014-01-01

    目的:观察新辅助化疗对不同病理类型的局部晚期非小细胞肺癌(NSCLC )肿瘤标记物、淋巴细胞亚群的影响。方法选取该院新辅助化疗的局部晚期NSCLC患者为研究对象,共计40例,选取20例体检的健康人群为对照组,比较不同病理类型的NSCLC肿瘤标记物癌胚抗原(CEA)、糖类蛋白-125(CA-125)、细胞角蛋白19可溶性片段(CYFRA21-1)的水平以及淋巴细胞亚群CD3+、CD4+、CD8+比例。分析不同疗效的NSCLC患者肿瘤标记物水平及淋巴细胞亚群的差异。结果(1)腺癌、鳞癌患者CEA、CA-125和CYFRA21-1水平均显著高于健康人群(P<0.05);鳞癌患者CEA升高水平低于腺癌,而鳞癌CA-125和CYFRA21-1升高水平高于腺癌(P<0.05);相对于健康人群,腺癌、鳞癌患者CD3+、CD4+、CD4+/CD8+均显著降低,而CD8+升高(P<0.05);但鳞癌、腺癌患者CD3+、CD4+、CD8+、CD4+/CD8+差异无统计学意义(P>0.05)。(2)经2个周期化疗后,缓解和部分缓解共18例,稳定和进展共22例。新辅助化疗有效的鳞癌患者血清CA-125和CYFRA21-1水平显著降低(P<0.05),新辅助化疗有效的腺癌患者血清CEA 和 CYFRA21-1水平显著降低(P<0.05)。新辅助化疗有效鳞癌、腺癌患者CD3+、CD4+、CD4+/CD8+升高,CD8+降低。结论不同病理类型的晚期NSCLC患者血清肿瘤标记物表达水平具有一定的差异,血清标记物与淋巴细胞亚群的变化均可作为评价新辅助化疗疗效的指标。%Objective To observe and analyze the effect of neoadjuvant chemotherapy on locally advanced non-small cell lung cancer tumor markers and lymphocyte subsets of different pathological type .Methods A total number of 40 NSCLC patients which received neoadjuvant chemotherapy and 20 normal people were selected in our study .To compare the differences of CEA ,CA-125 , CYFRA21-1 and

  1. 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

  2. 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