Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, dosing, and place in therapy of trifluridine–tipiracil are reviewed. Summary. Trifluridine–tipiracil is an oral antineoplastic agent consisting of trifluridine (a trifluorothymidine, a thymidine-based nucleoside analog) and tipiracil (a thymidine phosphorylase inhibitor), at a molar ratio of 1:0.5. Tipiracil blocks the degradation of trifluridine by thymidine phosphorylase, which improves the bioavailability of trifluridine and allows for oral administration. A Phase III study comparing trifluridine–tipiracil versus placebo in metastatic colorectal cancer (mCRC) patients refractory to or intolerant of standard therapy (n = 800) showed a benefit in overall survival (the primary endpoint) and progression-free survival compared with placebo. The most common grade ≥ 3 adverse events in trifluridine–tipiracil groups in Phase II and III trials were neutropenia, anemia, and leukopenia. The recommended dose of trifluridine–tipiracil is 35 mg/m2 twice a day after meals in a 28-day cycle comprising 2 weeks of 5 days of treatment and 2 days of rest (days 1-5 and 8-12 [every] 28 days), followed by 2 weeks of rest. Trifluridine–tipiracil is approved for the treatment of patients with mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an antivascular endothelial growth factor biological therapy and, if RAS wild-type, an antiepidermal growth factor receptor therapy. Conclusion. Trifluridine–tipiracil is a new treatment option for patients with mCRC who have received at least 2 prior lines of standard chemotherapy (including fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and an antiepidermal growth factor receptor antibody in patients with KRAS wild-type tumors). Ongoing trials are investigating trifluridine/tipiracil in combination with other anticancer agents for mCRC and its use in other malignancies, such as metastatic gastric cancer.
All Science Journal Classification (ASJC) codes
- Health Policy
- Colorectal neoplasms
- Drug combinations
- Oral administration