A phase II and pharmacokinetic study of first line S-1 for advanced gastric cancer in Taiwan
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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 m2, 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 AUC5–FU, and higher AUCFT and AUCOxo 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 AUC5–FU, AUCOxo may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.
KeywordsGastric cancer S-1 Chemotherapy Pharmacokinetic study Phase II
The authors wish to thank the centres and physicians participating in the study: National Taiwan University Hospital (Chih-Hung Hsu, M.D., Ph.D.); Veterans General Hospital, Taipei (Chung-Pin Li, M.D. Ph.D.); Chang-Gung Memorial Hospital, Linkou (Tsai-Shen Yang, M.D.); National Institute of Cancer Research, Tainan (Her-Shyong Shiah, M.D., Jang-Yang Chang, M.D.); Mackay Memorial Hospital, Taipei (Tsang-En Wang, M.D.); Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung (Chang-Ming Jan, M.D.). The study was funded by TTY Biopharm Co., Ltd., Taipei, Taiwan, and Taiho Pharmaceutical Co., Ltd., Tokyo, Japan.
Conflict of interest
Jen-Shi Chen, Yee Chao and Li-Tzong Chen received honoraria from TTY Biopharm Co., Ltd, Taipei, Taiwan. Li-Tzong Chen received research funding from TTY Biopharm Co., Ltd and Taiho Pharmaceutical Co., Ltd, Tokyo, Japan.
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