A phase I dose-escalation study of S-1 plus carboplatin in patients with advanced non-small-cell lung cancer

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin on day 1 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 5/65; level 2, 5/80; level 3, 6/80 [carboplatin (area under the curve, mg/ml/min)/S-1 (mg/m 2 /day)]. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle. Twelve patients were enrolled in this study. The main grade 3 or grade 4 toxicities observed during the first cycle were neutropenia (41%), thrombocytopenia (41 %) and transaminase elevation. Two of three patients in level 2 had dose-limiting toxicity and this level was considered the maximum tolerated dose. Level 1 was selected as the recommended dose. Objective responses were seen in four patients (response rate 33%). The combination of S-1 plus carboplatin is a feasible and well-tolerated regimen for the treatment of patients with advanced non-small-cell lung cancer.