Tegafur

Tegafur is a 5-FU prodrug (molecular formula:C8H9FN2O3) with good oral bioavailability. After oral administration, Tegafur is gradually converted to 5-FU in vivo, mainly by CYP2A6 enzyme activity in the liver. 5-FU is metabolised by the liver enzyme DPD. 5-FU is activated intracellularly by phosphorylation in its active metabolite 5-fluoro-deoxyuridine monophosphate (FdUMP). FdUMP and reduced folate are bound to the thymidylate synthase, resulting in the formation of a tertiary complex that inhibits DNA synthesis. In addition, 5-fluorouridine triphosphate (FUTP) is integrated into the RNA, which leads to a disturbance of the RNA functions.

Tegafur is given in combination with uracil, whereby the uracil inhibits the FU-degrading enzyme dihydropyrimidine dehydrogenase (DPD). Uracil has a higher affinity for DPD than 5-FU. The calcium folinate administered simultaneously enhances the cytotoxicity of 5-FU

Tegafur is approved for the treatment of metastatic colorectal tumors. A number of clinical studies are investigating further indications for this cytostatic drug (Li W et al. 2017)

300 mg/m2/day tegafur and 672 mg/m2/day uracil in combination with 90 mg/day calcium folinate in three ED perorally administered. Administered every eight hours (at least one hour before or one hour after meals). The therapy is administered on 28 consecutive days. Thereafter a seven-day break.

The main side effects in studies on Tegafur were mucositis and stomatitis, respectively. Note: The foot hand syndrome, which is an unpleasant side effect of the 5-FU prodrug capecitacin, is only observed to a small extent with Tegafur in combination with Uracil.

In case of hypersensitivity to the active substance or any of the other ingredients

Cave: Patients with partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency have an increased risk of severe toxicity when treated with fluoropyrimidines including 5-fluorouracil (5-FU) and its prodrugs capecitabine and tegafur. The following instructions should therefore be observed: Before starting treatment with fluoropyrimidines, the phenotype and/or genotype should be determined.

Treatment with drugs containing 5-FU, capecitabine or tegafur is contraindicated in patients with known complete DPD deficiency.

A reduced starting dose should be considered in patients with identified partial DPD deficiency.

In patients receiving continuous 5-fluorouracil infusions, therapeutic drug monitoring (TDM) of 5-fluorouracil may improve clinical outcomes.

1. Li W et al (2017) Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study. Oncotarget 8: 37826-37834.