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

BACKGROUND: TAS-102 consists of α, α, α-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...

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Detalles Bibliográficos
Autores principales: Doi, T, Ohtsu, A, Yoshino, T, Boku, N, Onozawa, Y, Fukutomi, A, Hironaka, S, Koizumi, W, Sasaki, T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405214/
https://www.ncbi.nlm.nih.gov/pubmed/22735906
http://dx.doi.org/10.1038/bjc.2012.274
Descripción
Sumario:BACKGROUND: TAS-102 consists of α, α, α-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). α, α, α-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.