Phase I study of vinorelbine and paclitaxel in small-cell lung cancer

Background: Vinorelbine and paclitaxel interfere with mitotic spindle function through different mechanisms of action. Both of the drugs show antitumor activity in small-cell lung cancer when used as single agents; furthermore, in vitro and in vivo studies have shown a synergistic activity between the two drugs. Patients and methods: Patients with small-cell lung cancer no longer amenable to conventional treatment were entered into a phase I study in which vinorelbine was given at a fixed dose of 30 mg/m² by 15-min intravenous infusion, whereas paclitaxel was given by 3-h infusion starting 1 h after vinorelbine at an initial dose of 90 mg/m², which was subsequently escalated by 30-mg/m² steps. Cycles were repeated every 21 days. Results: Grade 3 neutropenia was observed only in three patients treated at the fifty dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in three of five patients treated at the fifth dose level (paclitaxel 210 mg/m²). Other side effects were generally mild. The overall response rate in 22 evaluable patients was 32% (95% CI 13–51%); in particular, 1 complete response (4.5%) and 6 partial responses (27.3%) were observed. The maximally tolerated doses recommended for phase II studies are 180 mg/m² for paclitaxel and 30 mg/m² for vinorelbine. The observed myelosuppression was less severe than anticipated on the basis of the effects of each drug alone. Conclusions: The promising activity of this drug combination warrants a phase II study in untreated patients with extensive-stage small-cell lung cancer. Received: 9 February 1997 / Accepted: 9 June 1997