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Emerging combination therapies for metastatic colorectal cancer – impact of trifluridine/tipiracil

Authors Puthiamadathil JM, Weinberg BA

Received 22 July 2017

Accepted for publication 5 September 2017

Published 3 October 2017 Volume 2017:9 Pages 461—469


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel

Video abstract presented by Benjamin A Weinberg

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Jeevan M Puthiamadathil,1 Benjamin A Weinberg1,2

1Department of Medicine, 2Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

Abstract: Patients with metastatic colorectal cancer (mCRC) are surviving longer now than ever before, but mortality rates are still high and more effective therapies are clearly needed. For patients with disease that is refractory to fluoropyrimidines, oxaliplatin, irinotecan, and biologic agents targeting the vascular endothelial growth factor and epidermal growth factor receptor pathways, novel treatment options trifluridine/tipiracil (TAS-102) and regorafenib can be effective disease stabilizers. However, objective clinical responses are rare and toxicities are manageable but common. In order to tackle poor clinical responses to TAS-102, there is an ongoing effort to effectively combine this drug with other agents, particularly those targeting angiogenesis. Certain subpopulations appear to benefit more than others from TAS-102; those that benefit often have underlying genetic defects in DNA repair pathways and/or develop neutropenia. In this review, we focus on the role of TAS-102 in the treatment of mCRC, including its use in combination with other agents, potential predictive biomarkers of response to TAS-102, and possible future directions.

Keywords: metastatic colorectal cancer, trifluridine, tipiracil, TAS-102, regorafenib

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