Background: In this phase I/II trial, the maximum tolerated dose (MTD) and activity of vinorelbine administered in continuous infusion as first-line treatment for advanced non-small-cell lung cancer (NSCLC) was determined in 25 consecutive chemotherapy-naive patients with advanced NSCLC.
Patients and methods: Vinorelbine was administered as an initial intravenous (I.V.) bolus of 8 mg/m(2) on day 1 followed by a 4-day continuous I.V. infusion at 5 different 24-hour dose levels to be repeated every 21 days. All 25 patients (159 cycles) were evaluable for response. The MTD was 8 mg/m(2) bolus followed by a continuous I.V. infusion of 11 mg/m(2) per day over 4 days.
Results: The dose-limiting toxicities were febrile neutropenia in 6 patients and grade 3 mucositis in 2 patients. There was less neurotoxicity and constipation and more mucositis compared with the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Treatment responses were observed in 6 patients: 1 complete response and 5 partial responses. The overall response rate was 24% (95% confidence interval [CI], 8%-40%). Median time to progression was 4 months (95% CI, 2-11 months), and median survival was 6 months (95% CI, 2-18 months).
Conclusion: The results demonstrate that, in this setting of first-line treatment of NSCLC, vinorelbine administered as an 8 mg/m(2) bolus followed by a continuous infusion of 11 mg/m(2) per day over 4 days is the recommended schedule. Further trials are necessary to establish activity and possible benefits of combination with other agents.