Trifluridine/tipiracil: A practical guide to its use in the management of refractory metastatic colorectal cancer in Australia

Abstract

Trifluridine/tipiracil is available on the Australian Pharmaceutical Benefits Scheme for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, fluoropyrimidine-, oxaliplatin-and irinotecan-based chemotherapies, antivascular endothelial growth factor agents and anti-epidermal growth factor receptor agents. This article reviews trifluridine/tipiracil clinical data and presents practical information on its use in the management of refractory mCRC in Australia. Whereas the primary mechanism of action of fluoropyrimidines such as fluorouracil (5-FU) and capecitabine is enzyme inhibition of nucleotide synthesis, trifluridine/tipiracil primarily acts by incorporation into DNA, resulting in DNA dysfunction.Trifluridine/tipiracil has activity in patients with 5-FU-resistant tumors and can be considered in patients with prior intolerance or toxicity to 5-FU. In the pivotal phase III RECOURSE trial evaluating trifluridine/tipiracil in chemotherapy-refractory mCRC, efficacy benefits were observed across all a priori prognostic subgroups including those defined by age (≥65 and ≥75 years), geographical origin, primary tumor site or KRAS status. Trifluridine/tipiracil therapy benefits appropriately selected patients who have an ECOG performance status of 0 or 1, with no more than mild hepatic impairment or mild-to-moderate renal impairment, and who are capable of adhering to oral therapy safely. Appropriate dosing, monitoring for adverse events and effective management of side effects are essential.

Efficacy and tolerability of trifluridine/tipiracil in patients with refractory metastatic colorectal cancer at the general hospital of Šibenik-Knin country

“…The TERRA study confirmed that TT has a statistically significant survival benefit compared with placebo in Asian patients with mCRC refractory or intolerant to standard chemotherapies, regardless of exposure to biologic therapy. The safety profile is similar to previous reports (16)(17)(18). The primary endpoint in PRECON-NECT study was safety.…”

Pan-Cancer Molecular Patterns and Biological Implications Associated with a Tumor-Specific Molecular Signature

“…The top 3 enriched drugs were etoposide, monobenzone, and trifluridine. Etoposide is a chemotherapy agent used in multiple cancer types [ 79 ], while monobenzone combined with imiquimod induces antimelanoma immunity in cutaneous metastases [ 80 ], and trifluridine is used in metastatic colorectal cancers that are refractory to other therapies [ 81 ]. These results suggest potential repurposing of multiple drugs, showing that a specific subpopulation of some cancer types may be affected by drugs generally used on other cancer types.…”