PHASE-I STUDY OF VINORELBINE AND PACLITAXEL IN SMALL-CELL LUNG-CANCER

Background Vinorelbine and paclitaxel interfere with mitotic spindle f unction through different mechanisms of action. Both of the drugs show antitumor activity in small-cell lung cancer when used as single agen ts; furthermore, in vitro and in vivo studies have shown a synergistic activity between the two drugs. Patients and methods: Patients with s mall-cell lung cancer no longer amenable to conventional treatment wer e entered into a phase I study in which vinorelbine was given at a fix ed dose of 30 mg/m(2) by 15-min intravenous infusion, whereas paclitax el was given by 3-h infusion starting Ih after vinorelbine at an initi al dose of 90 mg/m(2), which was subsequently escalated by 30-mg/m ste ps. Cycles were repeated every 21 days, Results: Grade 3 neutropenia w as observed only in three patients treated al the fifty dose level. Th rombocytopenia never reached grade 3. Neurotoxicity was considered dos e-limiting, since grade 3 peripheral neuropathy occurred in three of f ive patients treated at the fifth dose level (paclitaxel 210 mg/m(2)). Other side effects were generally mild, The overall response rate in 22 evaluable patients was 32% (95% CI 13-51%). in particular, I comple te response (4.5%) and 6 partial responses (27.3%) were observed. The maximally tolerated doses recommended for phase II studies are 180 mg/ m(2) for paclitaxel and 30 mg/m(2) for vinorelbine. The observed myelo suppression was less severe than anticipated on the basis of the effec ts of each drug alone. Conclusions: The promising activity of this dru g combination warrants a phase II study in untreated patients with ext ensive-stage small-cell lung cancer.