[Phase I study of S-1. S-1 Study Group].
[Phase I study of S-1. S-1 Study Group].
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[S-1的第一阶段研究。
DOI：
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
I. Nakao
中科院分区：
文献类型：
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作者：
Tetsuo Taguchi;Y. Inuyama;Ryunosuke Kanamaru;K. Hasegawa;S. Akazawa;H. Niitani;H. Furue;Minoru Kurihara;K. Ota;S. Suga;Yutaka Ariyoshi;Shin;Takatoshi Shimoyama;T. Toge;Shigemitsu Takashima;K. Sugimachi;Y. Hara;H. Fujita;K. Kimura;Tsuyoshi Saito;Shigeru Tsukagoshi;I. Nakao
我们在全国16个机构进行了一项多中心研究，对一种新型口服抗肿瘤药物氟代嘧啶类药物S-1进行了I期研究，其中替加氟（FT）与两类调节剂5-氯-2，4-二羟基吡啶（CDHP）和氧羰基钾（Oxo）以FT：CDHP：Oxo = 1：0.4：1的摩尔比联合使用。评价了两种给药方法，每日一次和每日两次给药。因此，MAD分别确定为150 mg/只/天（约200 mg/只/天）和75 mg/只x2/天（约100 mg/只x2/天）。DLF是骨髓抑制，主要包括两次给药中的白细胞减少。观察到的大多数不良反应（包括骨髓抑制）在停药后消失，并在约2周内恢复。除骨髓抑制外，导致停药的不良反应为皮疹和呕吐。观察到的其他不良反应包括厌食、不适、腹泻和口腔炎。腹泻和口腔炎为轻度（1级），200 mg/只/天剂量组除外，未导致停药。基于这些结果和药代动力学评价，早期II期研究的推荐剂量和给药方式确定为75 mg/人每日两次给药，连续28天，停药14天（1个疗程）。
We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).