Combination therapy versus single agent chemotherapy in non-small cell lung cancer

There is proven evidence of improved symptom control with platinum-based chemotherapy in the palliation of non-small cell lung cancer, and small but definite improvements in progression-free and overall survival when compared with best supportive care. The newer chemotherapy agents vinorelbine, gemcitabine, docetaxel and paclitaxel all have single agent activity, and in combination with cisplatin these provide superior quality of life and/or survival compared with the single agents, albeit with some increase in haematological toxicity. Doublet chemotherapy consisting of a new agent combined with platinum, cisplatin by preference where tolerated, has become the standard of care for advanced disease. The use of a functional assessment of fitness, rather than chronological age alone, is appropriate in the treatment of elderly patients. Although in this group there is evidence that doublets are superior to single agents, treatment should be undertaken with caution. In the second line setting where patients are unlikely to tolerate combination therapy, single agents have proven superiority over best supportive care. Patients with poor performance status (PS2) without comorbidity may tolerate combination therapy, but currently available evidence is insufficient to allow a definitive recommendation for combination or single-agent chemotherapy.

[1]  G. Hillerdal,et al.  Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  K. Matsuo,et al.  Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  J. Pignon,et al.  Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. , 2004, JAMA.

[4]  L. Asmar,et al.  A phase II study of weekly docetaxel and carboplatin in stage IIIB (with effusion) or stage IV non-small cell lung cancer patients age <65 and performance status 2. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  I. Boukovinas,et al.  Gemcitabine (G) vs gemcitabine-carboplatin (GCB) for patients with advanced non-small cell lung cancer (NSCLC) and PS:2. A prospective randomized phase II study of the Hellenic Co-Operative Oncology Group , 2004 .

[6]  J. Crowley,et al.  Sequential vinorelbine (V) and docetaxel (D) in advanced non-small cell lung cancer (NSCLC) patients age > 70, or with performance status (PS) 2: A SWOG phase II trial (S0027) , 2004 .

[7]  M. Guida,et al.  Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients , 2004, British Journal of Cancer.

[8]  K. Syrigos,et al.  Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  T. Shanafelt,et al.  Are chemotherapy response rates related to treatment-induced survival prolongations in patients with advanced cancer? , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Miklos Pless,et al.  Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  R. Coffin,et al.  ImmunoVEXex vivo: A herpes simplex virus-based, dendritic cell-mediated anti-cancer vaccine platform , 2004 .

[12]  C. Gridelli,et al.  Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[13]  G. Giaccone,et al.  Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  C. Gridelli,et al.  Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  M. Vangel,et al.  O-49 Age-specific subanalysis of ECOG 1594: Fit elderly patietns (70–80 yrs) with NSCLC do as well as younger patients (<70) , 2003 .

[16]  P. Stephenson,et al.  O-52 ECOG 1599: Randomized phase II study of paclitaxel/carboplatin vs cisplatin/gemcitabine in performance status (PS) 2 patients with treatment-naive advanced NSCLC , 2003 .

[17]  A. Rossi,et al.  Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. , 2003, Journal of the National Cancer Institute.

[18]  S. Kudoh,et al.  Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer , 2003, British Journal of Cancer.

[19]  M. Dimopoulos,et al.  Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  G. Dranitsaris,et al.  Cost-effectiveness of chemotherapy for nonsmall-cell lung cancer , 2002, Current opinion in oncology.

[21]  David Cella,et al.  Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial. , 2002, Journal of the National Cancer Institute.

[22]  David Harrington,et al.  Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. , 2002, The New England journal of medicine.

[23]  N. Waugh,et al.  Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review , 2002, Thorax.

[24]  V. Georgoulias,et al.  Comparison of docetaxel/cisplatin to docetaxel/gemcitabine as first-line treatment of advanced non-small cell lung cancer: early results of a randomized trial. , 2001, Lung cancer.

[25]  V. Lorusso,et al.  Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase III trial. , 2001, Lung cancer.

[26]  J. Krook,et al.  Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594 , 2001, Cancer.

[27]  K. Nackaerts,et al.  Clinical-benefit response in advanced non-small-cell lung cancer: A multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  M. Aristides,et al.  PCN7: ECONOMIC EVALUATION OF GEMZAR AND BEST SUPPORTIVE CARE (BSC) RELATIVE TO BEST SUPPORTIVE CARE ALONE IN THE TREATMENT OF NON SMALL CELL LUNG (NSCLC) CANCER IN THE UK , 2001 .

[29]  C. Gridelli The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study. , 2001, The oncologist.

[30]  J. Bogaerts,et al.  Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  M. Ranson,et al.  Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. , 2000, Journal of the National Cancer Institute.

[32]  R. Stephens,et al.  Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer – a randomized trial with quality of life as the primary outcome , 2000, British Journal of Cancer.

[33]  M. Kris,et al.  Randomized Phase III Trial of Docetaxel Versus Vinorelbine or Ifosfamide in Patients With Advanced Non–Small-Cell Lung Cancer Previously Treated With Platinum-Containing Chemotherapy Regimens , 2000 .

[34]  J. Dancey,et al.  Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  V. Lorusso,et al.  Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  K. Roszkowski,et al.  A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). , 2000, Lung cancer.

[37]  R. Souhami,et al.  Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  J. Crowley,et al.  Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  R. Stahel,et al.  Single-agent gemcitabine versus cisplatin-etoposide: early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer. , 1997, Annals of oncology : official journal of the European Society for Medical Oncology.

[40]  J. Whang‐Peng,et al.  Gemcitabine versus the combination of cisplatin and etoposide in patients with inoperable non-small-cell lung cancer in a phase II randomized study. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  B. Hillner,et al.  Cost-effectiveness analysis of three regimens using vinorelbine (Navelbine) for non-small cell lung cancer. , 1996, Seminars in oncology.

[42]  O. Brodin,et al.  Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials , 1995 .

[43]  P Chomy,et al.  Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[44]  W. Gregory,et al.  Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  J. Holland,et al.  Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  M. Aristides,et al.  Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes. , 2005, Lung cancer.

[47]  M. Aristides,et al.  Retrospective cost analysis of gemcitabine in combination with cisplatin in non-small cell lung cancer compared to other combination therapies in Europe. , 2004, Lung cancer.

[48]  A. Gregor,et al.  Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  K. Dickersin,et al.  Single agent versus combination chemotherapy in patients with advanced nonsmall cell lung carcinoma , 1998, Cancer.