A phase I study of concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma

Objective: Chemoradiation based on S- 1, a novel oral antitumor agent of fluorinated pyrimidines, is the treatment for T2N0 glottic carcinoma; however, the optimal scheduling and dosing have still not been established. A phase I study was conducted to determine the maximum tolerated dose of S- 1 with radiotherapy of 2 Gy/ day for 5 days a week to a total dose of 60 Gy. Endpoints of this study were to examine the toxicity profile of this regimen and to determine the recommended dose of S- 1. Methods: Concomitant administration with the above- mentioned radiotherapy of S- 1 once a day for 2 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S- 1 60 mg/ body ( level 1) to 80 mg/ body/ day ( level 2), and then to 100 mg/ body/ day ( level 3). Results: Twenty- one patients were valid for safety. Eighteen patients were enrolled in the dose- escalation phase. In all patients, S- 1 was administered. The maximum tolerated dose was determined to be 100 mg/ body/ day and the dose-limiting toxicity was indicated by the onset of grade 3 chemoradiation dermatitis. Therefore, the determined recommended dose of S- 1 was 80 mg/ body/ day. Objective response according to Response Evaluation Criteria in Solid Tumors were observed in 20 of 21 patients who had measurable disease ( 95.2%). Conclusion: Concurrent S- 1 and radiotherapy was feasible and well tolerated, and was suggested to produce a worthwhile response in T2N0 glottic carcinoma. These results warrant further investigation, and a phase II has already been started. Copyright (C) 2006 S. Karger AG, Basel.