1094 A dose escalation study of carboplatin plus vinorelbine for advanced non-small cell lung cancer

Abstract

Platinum compounds and vinorelbine have been demonstrated to be active in non-small cell lung cancer (NSCLC). A dose-response relationship with platinum-based chemotherapy has been suggested for a number of malignancies including NSCLC. The aims of the study were to assess tolerability and optimal dose-intensity of increasing doses of carboplatin (300 mg/m 2 level 1, 350 mg/m 2 level 2, 400 mg/m 2 level 3, day 1) in association with a fixed dose of vinorelbine (25 mg/m 2 days 1 and 8) without G-CSF in advanced NSCLC. Thirty-eight patients entered the study and are evaluable for toxicity and response. Patients were untreated with systemic chemotherapy, had TNM stage IIIB–IV, performance status ECOG 0–2, and their median age was 62 years (range, 41‐70). The number of patients evaluable on each dose level was 14 (level 1), 14 (level 2) and 10 (level 3, current level). A total of 142 courses was delivered (median per patient, 4 courses). Non-hematologic side effects included grade I–II mucositis (8%), neurotoxicity (6%), and nausea (4%). No significant difference was observed for the 3 groups. The incidence of myelotoxicity was highest in the group of patients at level 3, with grade III–IV neutropenia observed in 20% of the cases and grade I–II thrombocytopenia in 30% of the patients, which was reversible and of short duration. No drug-related death has been observed, and only 1 patient at level 3 had a grade I infection. Objective remission was observed in 2/14 patients at level 1, in 3/14 patients at level 2, and in 3/10 patients at level 3. In conclusion, the combination of carboplatin at the dose of 400 mg/m 2 day 1 and vinorelbine at the dose of 25 mg/m 2 days 1 and 8 can be safely administered without G-CSF as first-line cytotoxic therapy for advanced NSCLC and warrants further evaluation.