The European Medicines Agency Review of Tegafur/Gimeracil/Oteracil (Teysuno™) for the Treatment of Advanced Gastric Cancer When Given in Combination with Cisplatin: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use (CHMP)

The product Teysuno™ (S‐1) contains tegafur, a prodrug of 5‐fluorouracil (5‐FU), and two modulators of 5‐FU metabolism, gimeracil and oteracil. The main clinical study in this application was a randomized controlled study comparing S‐1 plus cisplatin with 5‐FU plus cisplatin. In this study, median overall survival times of 8.6 months and 7.9 months for S‐1 plus cisplatin and 5‐FU plus cisplatin, respectively, were observed (hazard ratio, 0.92; 95% confidence interval, 0.80–1.05). The Committee for Medicinal Products for Human Use of the European Medicines Agency concluded that S‐1 in combination with cisplatin (75 mg/m2) was noninferior to 5‐FU plus cisplatin (100 mg/m2) in patients with advanced gastric cancer and adopted a positive opinion recommending the marketing authorization for this product for the treatment of advanced gastric cancer when given in combination with cisplatin. The recommended dose of S‐1 is 25 mg/m2 (expressed as tegafur content) twice a day, for 21 consecutive days followed by 7 days rest (one treatment cycle), in combination with 75 mg/m2 cisplatin i.v. administered on day 1. This treatment cycle is repeated every 4 weeks. The most common side effects reported in the pivotal study were anemia, neutropenia, vomiting, diarrhea, abdominal pain, weight decrease, anorexia, and fatigue. The objective of this paper is to summarize the scientific review of the application leading to approval in the EU. The full scientific assessment report and the summary of product characteristics are available on the European Medicines Agency website (http://www.ema.europa.eu). 摘要 药品Teysuno™（S‐1）包含替加氟，5‐氟尿嘧啶（5‐fluorouracil，5‐FU）的前体药物，和两种5‐FU代谢调节剂—吉美嘧啶和奥替拉西。 有关这一药品应用的主要临床研究是一项比较S‐1+顺铂与5‐FU+顺铂的随机对照研究。在这项研究中，S‐1+顺铂组与5‐FU+顺铂组的中位总生存时间分别为8.6个月与7.9个月（风险比0.92；95%可信区间[confidence interval，CI]，0.80∼1.05）。欧洲药品管理局人用药品委员会得出的结论为，对于晚期胃癌患者，S‐1联合顺铂（75 mg/m2）不劣于5‐FU联合顺铂（100 mg/m2），并采纳积极的意见，建议S‐1联合顺铂治疗晚期胃癌获得上市许可。S‐1的推荐剂量为25 mg/m2（以替加氟含量表示），每天2次，连续治疗21天后停药7天（1个治疗周期），并联合顺铂75 mg/m2，每个治疗周期的第1天i.v.给药。每4周重复一个治疗周期。 关键研究中所报告的最常见不良反应为贫血、中性粒细胞减少、呕吐、腹泻、腹痛、体重减轻、厌食和乏力。 本文旨在综述对申请材料进行的科学评审，该申请在EU获得核准。完整的科学评估报告和产品特征概述可访问欧洲药品管理局网站（http://www.ema.europa.eu）。 The scientific review of the application leading to the approval of Teysuno™ (S‐1) for the treatment of advanced gastric cancer when given in combination with cisplatin in the European Union is presented.