The safety and efficacy of trifluridine–tipiracil for metastatic colorectal cancer: A pharmacy perspective

Betty M. Chan, Howard S. Hochster, Heinz Josef Lenz

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)339-348
Number of pages10
JournalAmerican Journal of Health-System Pharmacy
Volume76
Issue number6
DOIs
StatePublished - Feb 21 2019

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Health Policy

Keywords

  • Colorectal neoplasms
  • Drug combinations
  • Oral administration
  • TAS-102
  • Tipiracil
  • Trifluridine

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