Phase I/II study of vinorelbine, mitomycin, and cisplatin for stage IIIB or IV non-small-cell lung cancer

Purpose: To determine the maximum-tolerated doses (MTDs) of vinorelbine (VRB), mitomycin (MMC), and cisplatin (P), given in two courses every 28 days to previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). Patients and Methods: At least three or four patients were entered at each dose level. The starting dose was 20 mg/m² for VRB on days 1 and 8 and 4 mg/m² for MMC on day 1, with a fixed dose of P 80 mg/m² on day 1 every 4 weeks. MMC was increased to 6 mg/m² at dose level 2 and subsequently to 8 mg/m² at dose level 4. At dose level 3, VRB was increased to 25 mg/m². Twenty-five patients were entered onto the phase I study and 19 patients were entered onto phase II study. Results: Nadir leukocyte and platelet counts decreased at each dose level. At dose levels 1 and 2, the dose-limiting toxicity (DLT) was not seen, but at dose levels 3 and 4, DLT was encountered in two patients. Nearly half the patients at dose level 4 had dose reduction due to grade 4 leukopenia. A mathematic model of all toxicity suggested that dose level 4 (VRB 25 mg/m² on days 1 and 8 and MMC 8 mg/m² and P 80 mg/m² on day 1, every 4 weeks) would be the recommended dose for phase II study at which grade 4 toxicity is expected in ≤ 25% of patients over two courses. Of the 25 assessable patients in the phase I study, 13 achieved a partial response and one had a complete response for a response rate of 56.0%. Of the 19 assessable patients in the phase II study, 12 had a partial response (63.2%; 95% confidence interval, 38.4% to 83.7%). Grade 3 and 4 leukopenia was observed in 19 (100%), and grade 3 thrombocytopenia was seen in seven (36.8%). Median survival time was 10.7 months and the 1-year survival rate was 43.2% in the 44 assessable patients. Conclusion: The VRB/MMC/P regimen is effective against NSCLC, and its efficacy should be confirmed through a randomized study.