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Crit Rev Oncol Hematol. 2016 Aug;104:91-7. doi: 10.1016/j.critrevonc.2016.05.015. Epub 2016 May 26.

Review on TAS-102 development and its use for metastatic colorectal cancer.

Author information

1
Division of Oncology, Instituto do Câncer do Estado de São Paulo, University of São Paulo, São Paulo, Brazil. Electronic address: mauricio@usp.br.
2
Division of Oncology, Instituto do Câncer do Estado de São Paulo, University of São Paulo, São Paulo, Brazil.

Abstract

TAS-102 is the combination of trifluridine (TFT) with tipiracil (TPI) in a 1:0.5 molar ratio. TFT is a fluoropyrimidine that retains cytotoxic activity in 5-fluorouracil resistant cell lines. Due to TFT short half-life, early clinical development was discouraging. Thereafter, TFT was shown to be promptly degraded by thymidine phosphorylase, also known as platelet-derived endothelial cell growth factor, a pro-angiogenic protein and a poor prognosis marker in colorectal cancer. TPI is a specific antagonist of thymidine phosphorylase and led to an increase in TFT serum levels when both agents are combined. Moreover, TPI is a potential anti-angiogenic molecule and could exert antitumor actions per se. TAS-102 was tested in several Phase I studies published in the early 21st century. The best regimen was settled as 70mg/m(2)/day, q12h, orally given at days 1-5 and days 8-13, each 28days. Recently, the first Phase III trial evaluating TAS-102 in refractory colorectal cancer patients was published. The RECOURSE trial demonstrated a survival advantage of the agent over supportive care, and definitely established TAS-102 as a novel strategy in the current armamentarium against colorectal cancer. Here we review the preclinical data regarding TFT and TPI that led to the development of TAS-102, and the set of clinical data that ultimately proved that TAS-102 improved outcomes in colorectal cancer patients.

KEYWORDS:

Colorectal cancer; Tas-102; Tipiracil; Treatment; Trifluridine

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