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Trifluridine/Tipracil

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Information about Trifluridine/Tipracil

Trifluridine/tipiracil is the combination of an antineoplastic pyrimidine analogue (trifluridine) with an inhibitor of its metabolism (tipiracil) that is used in the therapy of refractory, metastatic colorectal cancer. 

Liver toxicity

Trifluridine/tipiracil is associated with a low rate of transient serum enzyme elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury with jaundice. 

Mechanism of action of Trifluridine/Tipracil

Trifluridine (trye flure' i deen)/tipiracil (tye pir’ a sil) combines an antineoplastic pyrimidine analogue (2-deoxy-5-trifluoromethyl uridine) with a thymidine phosphorylase inhibitor that blocks its rapid metabolism, thus increasing the bioavailability of trifluridine.  Trifluridine is absorbed orally and converted intracellularly to a triphosphate which becomes incorporated into DNA causing inhibition of DNA synthesis, a decrease in cellular growth and proliferation and triggering apoptosis.  Trifluridine triphosphate is metabolized by thymidine phosphorylase which is inhibited by tipiracil, thus providing a longer half-life and increased intracellular concentrations of active phosphorylated trifluridine.  Trifluridine/tipiracil was shown to have potent activity in vitro in cellular and in vivo in animal models of colon cancer.  In clinical trials, this combination led to prolongation of progression-free as well as overall survival in patients with previously treated, refractory metastatic colorectal cancer

FDA approval information for Trifluridine/Tipracil

Trifluridine/tipiracil was approved for use in the United States in 2015 and is available in tablets of 15 mg/14 mg and 20 mg/19 mg under the commercial name Lonsurf. 

Clinical use of Trifluridine/Tipracil

Current indications are for refractory, metastatic colorectal cancer after previous treatment with other agents.  The recommended dose regimen is 35 mg/m2(based upon the trifluridine component) orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle. 

Side effects of Trifluridine/Tipracil

Common side effects include bone marrow suppression, weakness, fatigue, nausea, anorexia, diarrhea, abdominal pain and fever.  Less common, but potentially severe adverse events include severe myelosuppression, febrile neutropenia, infections, sepsis and embryo-fetal toxicity.

Alphabetic list of antineoplastic agents - 0-9 - A1 - A2 - A3 - A4 - A5 -A6 - B - C - D - E - F - G - H - I - JK - L - M - NO - PQ - R - S - T - UVW - XYZ

 

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