Development History and Concept of an Oral Anticancer Agent S-1 (TS-1®): Its Clinical Usefulness and Future Vistas
Development History and Concept of an Oral Anticancer Agent S-1 (TS-1®): Its Clinical Usefulness and Future Vistas
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口服抗癌剂S-1（TS-1®）的发展历史和概念：其临床用途和未来前景
DOI：
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发表时间：
2008
影响因子：
2.4
通讯作者：
T. Shirasaka
中科院分区：
文献类型：
--
作者：
T. Shirasaka
杜辛斯基等人。 5-氟尿嘧啶（5-FU）的发现给人类留下了伟大的礼物。从这一发现到 S-1 (TS-1®) 的开发已经过去了大约 50 年。开发一种同时具有增强疗效和减少不良反应作用的抗癌药物的概念只有通过三组分组合药物才能实现。 S-1 是一种口服抗癌剂，含有 5-FU 和替加氟 (FT) 两种生化调节剂，替加氟是一种代谢激活的 5-FU 前药。第一种调节剂 5-氯-2,4-二羟基吡啶 (CDHP) 通过有效抑制 5-FU 的降解来增强 5-FU 的药理作用。第二种调节剂氧酸钾 (Oxo) 口服后定位于胃肠道 (GI) 粘膜细胞，通过抑制胃肠道中 5-FU 的活化来降低胃肠道毒性的发生率。因此，S-1 以 1:0.4:1 的摩尔比结合 FT、CDHP 和 Oxo。 1999年至2007年，S-1被批准用于治疗以下七种癌症：胃癌、头颈癌、结直肠癌、非小细胞肺癌、乳腺癌、胰腺癌和胆道癌。提出“S-1 和低剂量顺铂治疗”，不会引起 3 级非血液学毒性，以增强其临床实用性。此外，“隔日 S-1 方案”可以利用其强烈的时间依赖性作用模式来改善 5-FU 的给药方案。前者的特点是骨髓毒性和非血液毒性（例如≤1级厌食、疲劳、口腔炎、恶心、呕吐和味觉改变）发生率低。这两种方法被认为可以实现 S-1 的长期治疗。
Dushinsky et al. left a great gift to human beings with the discovery of 5-fluorouracil (5-FU). Approximately 50 years have elapsed from that discovery to the development of S-1 (TS-1®). The concept of developing an anticancer agent that simultaneously possesses both efficacy-enhancing and adverse reaction-reducing effects could be achieved only with a three-component combination drug. S-1 is an oral anticancer agent containing two biochemical modulators for 5-FU and tegafur (FT), a metabolically activated prodrug of 5-FU. The first modulator, 5-chloro-2,4-dihydroxypyridine (CDHP), enhances the pharmacological actions of 5-FU by potently inhibiting its degradation. The second modulator, potassium oxonate (Oxo), localizing in mucosal cells of the gastrointestinal (GI) tract after oral administration, reduces the incidence of GI toxicities by suppressing the activation of 5-FU in the GI tract. Thus, S-1 combines FT, CDHP and Oxo at a molar ratio of 1:0.4:1. In 1999–2007, S-1 was approved for the treatment of the following seven cancers: gastric, head and neck, colorectal, non-small cell lung, breast, pancreatic and biliary tract cancers. ‘S-1 and low-dose cisplatin therapy’ without provoking Grade 3 non-hematologic toxicities was proposed to enhance its clinical usefulness. Furthermore, ‘alternate-day S-1 regimen’ may improve the dosing schedule for 5-FU by utilizing its strongly time-dependent mode of action; the former is characterized by the low incidences of myelotoxicity and non-hematologic toxicities (e.g. ≤Grade 1 anorexia, fatigue, stomatitis, nausea, vomiting and taste alteration). These two approaches are considered to allow long-lasting therapy with S-1.
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DOI：
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发表时间：
2001-10
期刊：
Gan to kagaku ryoho. Cancer & chemotherapy
影响因子：
--
作者：
Y. Inuyama;A. Kida;M. Tsukuda;N. Kohno;B. Satake
通讯作者：
Y. Inuyama;A. Kida;M. Tsukuda;N. Kohno;B. Satake
DOI：
10.1073/pnas.83.23.8923
发表时间：
1986-12-01
影响因子：
11.1
作者：
SCANLON, KJ;NEWMAN, EM;PRIEST, DG
通讯作者：
PRIEST, DG
影响因子：
45.3
作者：
Adjei, AA;Reid, JM;Erlichman, C
通讯作者：
Erlichman, C
影响因子：
1.8
作者：
Shimada, T;Yamazaki, H;Guengerich, FP
通讯作者：
Guengerich, FP