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Ref Type Journal Article
PMID (27126991)
Authors van der Velden DL, Opdam FL, Voest EE
Title TAS-102 for Treatment of Advanced Colorectal Cancers That Are No Longer Responding to Other Therapies.
Journal Vol Issue Date Pages Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research 22 12 2016 Jun 15 2835-9 Clin Cancer Res
URL
Abstract Text TAS-102 is a novel oral formulation of trifluridine (TFT) and tipiracil hydrochloride (TPI), a thymidine phosphorylase inhibitor. TFT was originally synthesized in the 1960s and is a nucleoside analogue that impedes DNA synthesis by inhibition of thymidylate synthase. TFT's main mechanism of action, however, seems to be its incorporation into DNA, which distinguishes TFT from current well-known antimetabolites like 5-fluorouracil (5-FU). The rapid degradation of TFT brought initial clinical development to a halt, but TFT reentered clinical trials when addition of a TPI was found to improve the bioavailability of TFT. The combined TFT-TPI formulation was tested in patients with treatment-refractory metastatic colorectal cancer in the randomized phase III RECOURSE study. Compared with placebo, TAS-102 was associated with an overall survival (OS) and progression-free survival (PFS) benefit and a 32% reduction in risk of death [median OS, 7.1 (95% CI, 6.5-7.8) vs. 5.3 months (95% CI, 4.6-6.0); median PFS, 2.0 (95% CI, 1.9-2.1) vs. 1.7 months (95% CI, 1.7-1.8); HR for death, 0.68 (95% CI, 0.58-0.81, P < 0.001)]. Based on the results of this pivotal trial and supported by results from an earlier phase II study, TAS-102 recently gained FDA approval. This article reviews the development of TAS-102 and its therapeutic value for the proposed indication. Clin Cancer Res; 22(12); 2835-9. ©2016 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References