Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, No 5, Fu-Hsing Street, Kwei-Shan Township, Taoyuan County 33305, Taiwan.
Cancer Chemother Pharmacol. 2011 Jun;67(6):1281-9. doi: 10.1007/s00280-010-1416-8. Epub 2010 Aug 17.
To evaluate the efficacy, safety and pharmacokinetic profiles of S-1, which composed of tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4-dihydroxypyridine and potassium oxonate (Oxo), in Taiwanese advanced gastric cancer (AGC) patients.
Patients with chemo-naïve, histologically confirmed AGC were eligible. S-1 was given orally at dose of 40, 50 or 60 mg, twice daily for patients with body surface <1.25, 1.25-1.5 and >1.5 m(2), respectively, on day 1-28 every 42 days/cycle.
Thirty-four patients were included. On intent-to-treat analysis, the overall response rate, median progression-free and overall survival were 35.3% [95% confidence interval (CI): 19.2-51.3%], 2.9 (95% CI: 2.4-5.8) months and 9.8 (95% CI: 6.1-NA) months, respectively. The most common grade 3-4 toxicities were anemia 23.5% and neutropenia 11.8%. There were two treatment-related mortality, which occurred in patients with suboptimal renal function underestimated by serum creatinine level at study entry. Single-dose pharmacokinetic study showed trend toward lower AUC(5-FU), and higher AUC(FT) and AUC(Oxo) comparing to most Western reports.
The efficacy, toxicity and pharmacokinetic profiles of S-1 in current study are compatible with those from other Asian populations. Accurate renal function assessment and more closely monitoring is mandatory for S-1 therapy in patients with low body mass. Literature review suggests that, besides AUC(5-FU), AUC(Oxo) may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.
评估替吉奥（S-1）在台湾地区晚期胃癌（AGC）患者中的疗效、安全性和药代动力学特征。
合格患者为未经化疗、组织学确诊的 AGC 患者。S-1 口服，体表面积<1.25、1.25-1.5 和>1.5 m2 的患者分别给予 40、50 或 60 mg，每日 2 次，第 1-28 天，每 42 天/周期。
共纳入 34 例患者。意向治疗分析显示，总缓解率、中位无进展生存期和总生存期分别为 35.3%（95%置信区间：19.2-51.3%）、2.9（95%置信区间：2.4-5.8）个月和 9.8（95%置信区间：6.1-未达到）个月。最常见的 3-4 级毒性为贫血 23.5%和中性粒细胞减少 11.8%。有 2 例治疗相关性死亡，均发生于研究入组时血清肌酐水平低估的肾功能欠佳患者。单次给药药代动力学研究显示，与大多数西方报告相比，S-1 的 AUC（5-FU）较低，AUC（FT）和 AUC（Oxo）较高。
S-1 在本研究中的疗效、毒性和药代动力学特征与其他亚洲人群相似。对于低体重患者，S-1 治疗时必须进行准确的肾功能评估和更密切的监测。文献回顾表明，除 AUC（5-FU）外，AUC（Oxo）也可能是亚洲和高加索人群对 S-1 依从性存在差异的原因。
