A novel antimetabolite: TAS-102 for metastatic colorectal cancer

ABSTRACT

TAS-102 is a new oral anti-tumor drug, composed of a thymidine-based nucleoside analog (trifluridine: FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride: TPI). TAS-102 has been shown to significantly improve overall survival and progression-free survival in patients with refractory metastatic colorectal cancer (mCRC) in placebo-controlled randomized phase II and III trials. The current review summarizes mechanisms of action, pharmacokinetics/dynamics and preclinical and clinical data of TAS-102 in colorectal cancer. TAS-102 is a new salvage-line treatment option for patients with mCRC. TAS-102 is well tolerated and has great potential in future clinical drug combination therapies.

KEYWORDS:

• TAS-102
• metastatic colorectal cancer
• chemotherapy
• refractory
• intolerant
• phase III
• salvage line

Financial & competing interests disclosure

H Baba has received research funding and honoraria from Taiho Pharmaceutical Co., Ltd. HJ Lenz has received clinical support from Taiho Pharmaceutical Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript and performed by Edanz Group Global Ltd and funded by Y Miyamoto.

Key issues

• TAS-102 is an oral anti-tumor drug, composed of a thymidine-based nucleoside analog (trifluridine: FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride: TPI), at a molar ratio of 1 : 0.5.

• TAS-102 demonstrated significant improvement in OS and PFS for patients with refractory mCRC in placebo-controlled randomized phase II and III trials.

• The most commonly reported adverse events of TAS-102 related to myelosuppression.

• TAS-102 is US FDA-approved for treatment of colorectal cancers that had previously been treated with fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab and/or EGF-receptor targeted therapy; and do not harbor KRAS mutations.