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Trifluridine Mechanism — SCE Medical Oncology MCQ

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ModerateGI CancersTrifluridine MechanismSCE Medical Oncology

A 55-year-old woman with metastatic CRC is prescribed trifluridine/tipiracil (TAS-102) third-line. She asks about the mechanism of action. What is the principal mechanism?

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Correct answer: E — Trifluridine is a thymidine-based nucleoside analogue incorporated into DNA causing strand breaks; tipiracil inhibits thymidine phosphorylase to prevent trifluridine degradation

Trifluridine/tipiracil (Lonsurf/TAS-102) combines two components: trifluridine (a thymidine-based nucleoside analogue that is incorporated into DNA, causing DNA dysfunction) and tipiracil (a thymidine phosphorylase inhibitor that prevents trifluridine degradation, maintaining plasma levels). It differs from 5-FU in mechanism: 5-FU primarily inhibits thymidylate synthase, while trifluridine's anti-tumour effect is primarily through direct DNA incorporation. The RECOURSE trial demonstrated OS benefit in refractory mCRC.

Reference: NICE TA405 Trifluridine/tipiracil; BNF; RECOURSE Mayer et al NEJM 2015