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TAS-102 for Treatment of Advanced Colorectal Cancers that Are No Longer Responding to Other Therapies.

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Published:25th Mar 2020
Author: van der Velden DL, Opdam FL, Voest EE.
Ref.:Clin Cancer Res. 2016 Apr 28. pii: clincanres.2783.2016. [Epub ahead of print]
DOI:10.1158/1078-0432.CCR-15-2783

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 analog 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 re-entered clinical trials when addition of a TPI was found to improve the bio-availability 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 to placebo, TAS-102 was associated with an overall and progression free survival 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.

 

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