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

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