Phase I/II study of gemcitabine plus vinorelbine in non-small cell lung cancer

Background: Because gemcitabine and vinorelbine have demonstrated single-agent activity in non-small cell lung cancer (NSCLC), we conducted this phase I/II study to determine the maximum tolerated dose (MTD) and activity of these drugs combined. Patients and methods: Patients with inoperable or advanced NSCLC and no prior chemotherapy were treated with gemcitabine plus vinorelbine on days 1 and 8 every 21 days. The initial doses of gemcitabine 1,000 mg/m(2) and vinorelbine 25 mg/m(2) were escalated by 250 mg/m(2) and 5 mg/m(2) respectively, in separate patient cohorts until the MTD was established. Results: In phase I, 32 patients received a total of 115 cycles. Dose-limiting toxicities were neutropenia and hepatotoxicity, occurring at the dose level of 1,500 mg/m(2) and 30 mg/m(2). Thus, the MTD used for phase II was 1,250 mg/m(2) and 30 mg/m(2). Of 41 patients in phase II, 16 (39%) achieved objective responses (95% confidence interval [CI] 24% to 54%), with a median time to progression of 4.2 months. Overall survival was 9 months (95% CI 5.7 to 12.7 months) and the 1-year survival rate was 31%. World Health Organization (WHO) greater than or equal to grade 3 neutropenia and reversible thrombocytosis occurred in 15% and 65% of patients, respectively. Non-hematologic toxicity was mild at all dose levels. Grades 3 and 4 hepatotoxicity were reported in one patient each. Conclusion: The combination of 1,250 mg/m(2) gemcitabine and 30 mg/m(2) vinorelbine on days 1 and 8 every 21 days is well tolerated and active in patients with NSCLC. These results should be confirmed in comparative studies.