A Phase I Study of Concurrent Chemoradiotherapy with S-1 for T2N0 Glottic Carcinoma

Abstract

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.

Induction Therapy with S-1 for Spindle Cell Carcinoma of the External Auditory Canal

“…There have been several reports about the administration of S-1 as adjuvant chemotherapy for head and neck cancer. One report recommended that S-1 should be administered at a dose of 60 mg/m 2 /day for 5 days, followed by 2 days off, in combination with irradiation (total dose: 64-70 Gy) for 6-7 weeks [12], while another study recommended that S-1 should be administered every day at a dose of 80-100 mg/body/day for 2 weeks and then suspended for 1-2 weeks to allow radiotherapy to be performed (total dose: 60-70.2 Gy) [13,14]. On the basis of the results of these studies, we chose a treatment regimen in which S-1 was delivered at a dose of 80 mg/body/day every day for 2 weeks before surgery.…”

Two elderly patients with advanced maxillary gingival carcinoma with complete response to concurrent radiotherapy and S-1 chemotherapy

“…[6][7] Moreover, it has been reported that concurrent radiotherapy and S-1 chemotherapy is effective 14 for oral SCC and for other cancers, including hypopharyngeal, glottic, urachal, pancreatic, and gastric. [18][19][20][21][22][23] Recently, Tsukuda et al reported that 2 weeks of S-1 followed by a 1-week rest period was more feasible for adjuvant chemotherapy of locoregionally advanced squamous cell carcinoma of the head and neck region than 4 weeks of S-1 followed by a 2-week rest period. 24,25 Therefore, we selected 2 weeks of S-1 followed by a 1-week rest period as the regimen for our patients.…”

Phase I Study of Oral S-1 and Concurrent Radiotherapy in Patients with Head and Neck Cancer

“…Tsuji et al reported the results of an S-1 dose escalation study with 2 weeks of S-1 administration followed by 2 weeks off S-1, and then 2 more weeks of S-1 administration during radiotherapy (total dose: 60 Gy). They reported that the recommended dose (RD) of S-1 was 80 mg/body/day with their schedule [15]. Sato et al reported that the RD of S-1 was 65 mg/m 2 /day when radiation was given to a total dose of 60 Gy and S-1 was administered every day for 2 weeks and then was suspended for 1 week [16].…”