Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours

被引：82

作者：

Doi, T. ^{[1
]}

Ohtsu, A. ^{[1
]}

Yoshino, T. ^{[1
]}

Boku, N. ^{[2
]}

Onozawa, Y. ^{[2
]}

Fukutomi, A. ^{[2
]}

Hironaka, S. ^{[2
]}

Koizumi, W. ^{[3
]}

Sasaki, T. ^{[3
]}

机构：

[1] Natl Canc Ctr Hosp E, Dept Gastroenterol & Gastrointestinal Oncol, Kashiwa, Chiba 2778577, Japan

[2] Shizuoka Canc Ctr Hosp, Div Gastrointestinal Oncol, Nagaizumi, Shizuoka 4118777, Japan

[3] Kitasato Univ E Hosp, Dept Internal Med, Minami Ku, Sagamihara, Kanagawa 2288520, Japan

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 107卷 / 03期

关键词：

phase I study; pharmacokinetics; TAS-102; TFT; TPI; COMBINATION ANTIMETABOLITE; FLUORINATED PYRIMIDINES; DEOXYRIBONUCLEIC-ACID; 5-TRIFLUOROMETHYL-2-DEOXYURIDINE; SCHEDULE; CANCER; CELLS;

D O I：

10.1038/bjc.2012.274

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: TAS-102 consists of a, a, a-trifluorothymidine (TFT) and an inhibitor of thymidine phosphorylase (TPI). We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours. METHODS: TAS-102 was administered twice daily on days 1-5 and days 8-12 in a 28-day cycle to patients with solid tumours refractory to standard chemotherapy, to determine its maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics (PKs). MTD was evaluated in cycle 1. RESULTS: Safety and PKs were evaluated in 21 patients treated with TAS-102 at 30, 40, 50, 60, or 70 mg m(-2) per day. DLTs, such as grade 4 leucopenia, grade 4 neutropenia, and grade 4 thrombocytopenia, were observed in two patients at doses of 30 and 70 mg m(-2). alpha,alpha,alpha-trifluorothymidine and TPI exposures increased dose dependently, and the percentage of decrease in neutrophil count and TFT exposure were significantly correlated. The disease control rate was 50.0% with a median progression-free survival of 2.4 months in 18 colorectal cancer patients. The dose of TAS-102 was not increased above 70 mg m(-2) per day because of the increased tendency for grade 3 and 4 neutropenia, and 70 mg m(-2) per day was the recommended dose for phase II studies. CONCLUSIONS: TAS-102 at 70 mg m(-2) per day was tolerated in Japanese patients with advanced solid tumours. Phase II studies are ongoing in patients with colorectal cancer. British Journal of Cancer (2012) 107, 429-434. doi: 10.1038/bjc.2012.274 www.bjcancer.com Published online 26 June 2012 (C) 2012 Cancer Research UK

引用

页码：429 / 434

页数：6

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