A Multi-Institution Phase I/II Trial of Triweekly Regimen with S-1 Plus Cisplatin in Patients with Advanced Non-small Cell Lung Cancer

Introduction: To determine the dose-limiting toxicity and recommended dose (RD) of cisplatin (CDDP) combined with S-1 (tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate) for patients with non-small cell lung cancer and to evaluate efficacy and toxicity of this regimen at RD. Methods: Patients with stages III and IV non-small cell lung cancer received 3-week cycles of treatment, each consisting of oral administration of S-1 at 80 mg/m(2) in 2 divided doses per day for 14 consecutive days, intravenous administration of CDDP (60 mg/m(2), 70 mg/m(2), or 80 mg/m(2)) on the first day, and no medication during the subsequent 7 days. The primary objective of phase I study was to estimate the maximum tolerable dose and the RD, and the primary end point of phase II study was response. Results: RD of CDDP in the analysis of 18 eligible patients was 60 mg/m(2). Evaluation of efficacy and toxicity at RD in 55 eligible patients showed that partial response was observed in 18 patients (32.7%, 95% confidence interval: 20.7-46.7%). The median survival time was 18.1 months, and the time to disease progression was 3.8 months. Grade 3 or severer adverse events were observed in 27 patients (49.1%). Conclusions: CDDP combined with S-1 showed a satisfactory overall survival time and acceptable toxicity profile. However, the response as the primary end point did not reach the predetermined threshold level.