Two phase I, pharmacokinetic (PK) and pharmacodynamic (PD) studies of TAS-109, a novel nucleoside analogue with 14 days and 7 days continuous infusion (CI) schedules
| Autor: | Alain C. Mita, C. H. Takimoto, J. Rodon, Scott Kopetz, T. Toko, K. Arakawa, K. Burns, Rosni Adinin, K. K. Sankhala, H. Q. Xiong |
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| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 26:2577-2577 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2008.26.15_suppl.2577 |
| Popis: | 2577 Background: TAS-109 is a novel deoxycitidine analogue with unique mechanism of action. Brief exposure to high concentrations of TAS-109 inhibits DNA polymerase resulting in S-phase arrest, while prolonged exposure to TAS-109 at low concentration causes DNA fragmentation, G2/M phase arrest and apoptosis. TAS-109 demonstrated activity in tumor xenografts resistant to other deoxycitidine analogs. Methods: Two phase I studies assessed the safety, PK, PD and preliminary efficacy of TAS-109. Patients (pts) with refractory solid tumors received TAS-109 CI 14 days on/7 days off (study-1) and 7 days on/7 days off (study-2). Enrollment required age > 18 yrs, ECOG Performance Status 0–2 and adequate organ function. Tumor response was assessed by RECIST criteria. Plasma was sampled for PK. PD studies utilized the Comet assay for study-2, allowing quantification of DNA strand breaks. Results: 29 pts were dosed in both studies. In study-1 (15 pts), dose limiting toxicities (DLT) consisting of febrile neutropenia (... |
| Databáze: | OpenAIRE |
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