Phase I/II study of gemcitabine plus vinorelbine as first-line chemotherapy of non-small-cell lung cancer.

ABSTRACT

PURPOSE: To determine the maximum-tolerated dose of gemcitabine when combined with a fixed dose of vinorelbine in the treatment of non-small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the activity of this combination. PATIENTS AND METHODS: Sixty-eight patients with stage IIIB/IV NSCLC were treated with vinorelbine at fixed dose of 30 mg/m(2) intravenously and gemcitabine at increasing dose levels from 800 to 1,500 mg/m(2) intravenously on days 1 and 8 every 3 weeks. RESULTS: In phase I, dose-limiting toxicity occurred at the dosage of 1,500 mg/m(2) gemcitabine, with three of five patients developing grade 4 thrombocytopenia. In phase II, with gemcitabine at 1,200 mg/m(2), 19 (36%) of 52 assessable patients responded. Objective response was observed in 11 (39%) of 28 patients with stage IIIB disease and in eight (33%) of 24 patients with stage IV. The median time to progression was 29 weeks (range, 2 to 41 weeks; 35 weeks and 16 weeks for stages IIIB and IV, respectively), and median survival was 54 weeks (range, 2 to 84+ weeks; 63 weeks and 42 weeks for stages IIIB and IV, respectively). One-year survival was 64% for patients with stage IIIB disease and 29% for those with stage IV. Clinical benefit response was observed in 29 (59%) of 49 assessable patients. Grade 4 leukopenia and thrombocytopenia were uncommon (6% and 8% of cases, respectively); however, grade 3/4 leukothrombocytopenia occurred more frequently in patients aged more than 70 years (52% and 24%, respectively). CONCLUSION: The combination of vinorelbine and gemcitabine is effective and tolerable in the treatment of NSCLC, thus deserving randomized trials with cisplatin combination regimens.