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 By Cesare Gridelli, Ciro Gallo, Frances A. Shepherd, Alfonso Illiano, Francovito Piantedosi, Sergio Federico Robbiati, Luigi Manzione, Santi Barbera, Luciano Frontini, Enzo Veltri, Brian Findlay, Silvio Cigolari, Robert Myers, Giovanni P. Ianniello, Vittorio Gebbia, Giampietro Gasparini, Sergio Fava, Vera Hirsh, Andrea Bezjak, Lesley Seymour, and Francesco Perrone Purpose: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non–small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient’s quality of life (QoL). This trial aimed to assess whether a combi- nation of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. Patients and Methods: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly as- signed gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cis- platin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. Results: Five hundred one patients were randomly as- signed to treatment. The median age was 62 years. There were no significant differences in global QoL scores be- tween the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Me- dian survival was 38 v 32 weeks and median progression- free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. Conclusion: Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin- based chemotherapy. There is a nonsignificant slight sur- vival advantage with cisplatin-based chemotherapy. Gem- Vin could be offered to advanced NSCLC patients who express concern about toxicity. J Clin Oncol 21:3025-3034. © 2003 by American Society of Clinical Oncology. E PIDEMIOLOGIC ESTIMATES for the year 2000 showed that lung cancer was the most common cancer in the world, both in terms of incidence (with 1.2 million new cases corre- sponding to 12.3% of the world total) and mortality (with 1.2 million deaths corresponding to 17.8% of the total). 1 Although incidence and death rates have stabilized and are slowly decreasing, especially among males, it is expected that lung cancer will continue to be a health issue of critical importance for decades to come. Older platinum-based (Pt-based) combination therapies pro- long survival modestly compared with best supportive care in patients affected by advanced non–small-cell lung cancer (NSCLC). 2 Recently, several new chemotherapeutic agents (pac- litaxel, gemcitabine, docetaxel, vinorelbine, and irinotecan) have shown good single-agent activity. In randomized phase III trials, these agents in combination with a platinum compound have been associated with improved quality of life (QoL) and im- proved survival of 8 to 10 months. 3 Recent randomized studies indicate that there are no significant differences in efficacy among several combinations of cisplatin with the new drugs, although they have shown varying profiles of toxicity. 4,5 Cisplatin is associated with more toxicity than other drugs used to treat NSCLC. In addition to nausea and vomiting, which can be partially controlled with antiemetic therapy, cisplatin causes cumulative neuropathy as well as profound fatigue, ototoxicity, and renal toxicity. Some patients are unable to tolerate the drug and thus tend to terminate treatment early. The combination of GemVin showed additive effects when it was tested in experimental models. 6 This nonplatinum regimen, From the GEMVIN Investigators, Naples, Italy; and the National Cancer Institute of Canada Clinical Trials Group, Kingston, Canada. Submitted June 17, 2002; accepted May 9, 2003. Partially supported by Clinical Trials Promoting Group (CTPG), Naples, Italy. The National Cancer Institute of Canada Clinical Trials Group received a grant from Eli Lilly Canada. The coordinating center (Clinical Trials Unit of the National Cancer Institute of Naples) is supported by Associazione Italiana per la Ricerca sul Cancro (AIRC). Cesare Gridelli is member of the speaker’s bureau for Eli-Lilly (Florence, Italy), Pierre-Fabre (Cedex, France), GlaxoSmithKline (Research Triangle Park, NC, USA); Ciro Gallo received honoraria from Glaxo-Smith Kline (Verona, Italy); Frances Shepherd received research funding and honoraria from Eli-Lilly (Scarborough, Ontario, Canada); Francesco Perrone received honoraria from Glaxo-Smith Kline (Verona, Italy). Address reprint requests to Cesare Gridelli, Clinical Trials Unit, National Cancer Institute, Via M Semmola; 80131 Naples, Italy; email: cgridelli@libero.it. © 2003 by American Society of Clinical Oncology. 0732-183X/03/2116-3025/$20.00 3025 Journal of Clinical Oncology, Vol 21, No 16 (August 15), 2003: pp 3025-3034 DOI: 10.1200/JCO.2003.06.099 Information downloaded from jco.ascopubs.org and provided by at University Health Network on August 12, 2015 from 199.212.7.70 Copyright © 2003 American Society of Clinical Oncology. All rights reserved.