Inuyama Y, Kida A, Tsukuda M, Kohno N, Satake B
Dept. of Otolaryngology, Hokkaido University School of Medicine.
Gan To Kagaku Ryoho. 1998 Jul;25(8):1151-8.
In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.
在开发新型抗癌药物时，最重要的是平衡抗肿瘤活性和毒性。为了实现高活性和低毒性，设计了S-1，其中5-氟尿嘧啶（5-FU）的前体药物替加氟与两类调节剂相结合。分别是肝内5-FU降解抑制剂CDHP和消化道内5-FU磷酸核糖基化抑制剂奥替拉西钾（Oxo）。1994年1月至1996年3月在日本，与全国15家机构合作开展了此项研究，以评估S-1对晚期头颈癌患者的抗肿瘤活性和毒性。26例患者中，1例完全缓解（CR），11例部分缓解（PR），缓解率为46.2%，3级不良事件如下：血红蛋白血症（7.7%）、白细胞减少、中性粒细胞减少、口腔炎和厌食（各3.8%）。未观察到4级不良事件和与治疗相关的死亡。基于这些发现，得出结论：S-1是一种治疗晚期头颈癌患者毒性较低的有用抗癌药物，临床前研究中发现的CDHP和Oxo的作用可能也体现在这些结果中。
