Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: A phase II randomized study of the Southern ItalyCooperative Oncology Group

Purpose: In a previous phase I study cisplatin (CDDP), gemcitabine (GEM), a nd vinorelbine (VNR) combination therapy was safe and very active in patien ts with non-small-cell lung cancer (NSCLC). This study was aimed at better defining the activity and toxicity of this regimen. Patients and Methods: One hundred eleven chemotherapy-naive patients, age l ess than or equal to 70 years, with stage IIIB or IV NSCLC and a performanc e status of 0 or 1 (Eastern Cooperative Oncology Group scale) were randomiz ed to two treatment arms. Patients on arm A received CDDP 50 mg/m(2), GEM 1 ,000 mg/m(2), and VNR 25 mg/m(2) on days 1 and 8 of an every-3-weeks cycle (57 patients). Patients on arm B received CDDP 80 mg/m(2), epirubicin 80 mg /m(2), and vindesine 3 mg/m(2), all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients). In December 1996, randomization was stopped early, and an additional 30 patients were treate d with the experimental regimen to obtain a more accurate estimation of its activity rare. Results: Among 87 patients who received the CDDP-GEM-VNR combination, four complete responses (CRs) and 46 partial responses (PRs) were observed, for an overall response rate of 57% (95% confidence interval [CI], 46% to 68%). Two CRs and 18 PRs were recorded among 54 patients on arm B, giving a 37% activity rate (95% CI, 24% to 51%). After a median follow-up duration of 19 months, the median progression-free and overall survival durations were 32 and 50 weeks in arm A, and 18 and 33 weeks in arm B, respectively. World H ealth Organization grade 3 to 4 neutropenia and thrombocytopenia occurred i n 46% and 14% of patients in arm A and in 22% and 11% of those in arm B, re spectively. Severe nonhematologic toxicity was uncommon in both arms. Conclusion: The CDDP-GEM-VNR combination is a highly effective treatment fo r patients with advanced NSCLC and has a manageable toxicity A phase III tr ial comparing this new combination with both CDDP-VNR and CDDP-GEM regimens is underway J Clin Oncol 17:1526-1534. (C) 1999 by American Society of Cli nical Oncology.