An Exhaustive Monograph on TAS-102 (Trifluridine/Tipiracil; Lonsurf®): Chemical Profile, Pharmacology, Clinical Efficacy, and Regulatory Status

I. Executive Summary & Introduction to TAS-102 (Lonsurf®)

A. Overview

TAS-102, marketed under the brand name Lonsurf®, is a novel, orally administered combination antineoplastic agent that has emerged as a cornerstone therapy for patients with heavily pre-treated, refractory metastatic gastrointestinal cancers.[1] Its development and approval represent a significant advancement in the management of metastatic colorectal cancer (mCRC) and metastatic gastric cancer (mGC), offering a new therapeutic option for a patient population with limited alternatives following progression on standard chemotherapeutic and biological regimens.[3]

B. Core Components

The drug product is a fixed-dose combination of two distinct active pharmaceutical ingredients, formulated in a precise molar ratio to achieve a synergistic therapeutic effect.[2] The components are:

• Trifluridine (FTD): A thymidine-based nucleoside analog, specifically α,α,α-trifluorothymidine, which functions as the primary cytotoxic component of the combination. Its mechanism is centered on the disruption of DNA synthesis and integrity.[1]
• Tipiracil (TPI): A specific and potent inhibitor of the enzyme thymidine phosphorylase (TP). Tipiracil is not included for any direct antineoplastic activity of its own; rather, its role is exclusively to modulate the pharmacokinetics of trifluridine, thereby enabling its therapeutic efficacy.[6]

C. Clinical Significance