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%).


CONCLUSIONS
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.
Tsuji
Hiroyuki
H
Department of Otolaryngology, Kanazawa Medical University, Ishikawa, Japan. tsujih-i@kanazawa-med.ac.jp
Kiba
Takayoshi
T
Nagata
Motoki
M
Inoue
Toshiya
T
Yukawa
Hisaya
H
Yamashita
Toshio
T
Shimode
Yuzo
Y
Murata
Hideyuki
H
Nagata
Kenji
K
Tomoda
Koichi
K
D000328:Adult; D000368:Aged; D003872:Dermatitis / Q000209:etiology; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D005931:Glottis / Q000473:pathology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid