Hirata Koichi, Horikoshi Noboru, Tominaga Kazusaku, Sohma Keisuke, Yamaguchi Koji, Okazaki Minoru, Furuhata Tomohisa, Sasaki Kazuaki, Nakano Yasuyuki, Ishizuka Hikaru, Yamada Yasuhide, Uno Shinji, Taguchi Tetsuo, Yamamitsu Susumu, Shirasaka Tetsuhiko
Dept of Surgery (Section 1), Sapporo Medical University, Japan.
Gan To Kagaku Ryoho. 2006 Jun;33 Suppl 1:27-35.
S-1 is an attractive oral fluorouracil antitumor drug, which is being called "a self-rescuing drug". This novel oral fluoropyrimidine is combined with three pharmacological agents: tegafur (FT) which is a prodrug of 5-fluorouracil (5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP) which inhibits dihydropyrimidine dehydrogenase (DPD) activity, and potassium oxonate (Oxo) which reduces gastrointestinal toxicity. Phase I and an early phase II clinical trials were performed about ten years ago, and these results had already been introduced to the Journal "Clinical Cancer Research Vol. 5, pages 2000-2005, 1999". The data of this article in this journal was referred from the results of the figures and tables based on the above trial. Most of the authors in this article have contributed on that pharmacokinetics study and published the above manuscripts. In that study, the pharmacokinetics of 5-FU, intact FT, CDHP and Oxo after administration of the standard dose of S-1 had been performed. These studies were carried out at two hospitals, Department of Surgery (Section 1) Sapporo Medical University and Chemotherapy Cancer Center, Cancer Institute Hospital and Japanese Foundation for Cancer Research (Ohtsuka). The number of patients accepted for this trial is twelve, 5 patients with gastric cancer, 4 with colorectal cancer and 3 with breast cancer. Single administration trial was referred to all patients, but consecutive administration trial was limited to ten patients. The results of plasma concentration, Cmax, Tmax, AUC0-14, and T1/2 of 5-FU, FT, CDHP, and Oxo were ascertained in details. It was a surprise that the indicated data was very similar to that of the intravenous 5-FU continuous infusion. Therefore, the low dose administration of 5-FU (FT) as S-1 may result in good antitumor effects with minimum adverse effects to the patients.
S-1是一种颇具吸引力的口服氟尿嘧啶类抗肿瘤药物，被称作“自救药物”。这种新型口服氟嘧啶与三种药理活性剂组合而成：替加氟（FT），它是5-氟尿嘧啶（5-FU）的前体药物；5-氯-2,4-二羟基吡啶（CDHP），可抑制二氢嘧啶脱氢酶（DPD）活性；以及奥索酸钾（Oxo），可降低胃肠道毒性。大约十年前进行了I期和早期II期临床试验，这些结果已发表在《临床癌症研究》杂志第5卷，第2000 - 2005页，1999年。该杂志上这篇文章的数据源自上述试验的图表结果。本文的大多数作者都参与了该项药代动力学研究并发表了上述手稿。在该研究中，对标准剂量S-1给药后5-FU、完整的FT、CDHP和Oxo的药代动力学进行了研究。这些研究在两家医院开展，分别是北海道医科大学外科（第1科室）以及癌症研究所医院和日本癌症研究基金会（大冢）化疗癌症中心。接受该试验的患者有12名，其中5名胃癌患者，4名结直肠癌患者和3名乳腺癌患者。所有患者均参与了单次给药试验，但连续给药试验仅限于10名患者。详细测定了5-FU、FT、CDHP和Oxo的血浆浓度、Cmax、Tmax、AUC0 - 14以及T1/2的结果。令人惊讶的是，所示数据与静脉注射5-FU持续输注的数据非常相似。因此，以S-1形式低剂量给药5-FU（FT）可能会在对患者产生最小不良反应的情况下带来良好的抗肿瘤效果。
