Tegafur/uracil + calcium folinate in colorectal cancer: double modulation of fluorouracil

Drugs. 1999:58 Suppl 3:77-83. doi: 10.2165/00003495-199958003-00011.

Abstract

The oral chemotherapeutic agent tegafur/uracil (UFT) is the first of a new class of anticancer drugs called dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines. Tegafur/uracil combines uracil with the fluorouracil prodrug tegafur in a 4:1 molar ratio. Uracil competitively inhibits the degradation of fluorouracil, which results in the concentration of fluorouracil remaining at sustained levels in both plasma and tumour. Tegafur/uracil has been commercially available in Japan since 1983 and examined extensively in various tumours. Trials conducted in the US have focused on the combination of tegafur/uracil plus calcium folinate (calcium leucovorin) [ORZEL]. Several phase I and II trials have evaluated the maximum tolerated dose, pharmacokinetics, efficacy, and safety of this combination in the treatment of colorectal cancer. Results have shown that tegafur/uracil at 300 mg/m2/day in divided doses given every 8 hours for 28 days provides prolonged exposure to fluorouracil. Furthermore, tegafur/uracil + calcium folinate is well tolerated, with dose-limiting toxicity manifesting as diarrhoea. Compared with intravenous fluorouracil plus folinic acid (leucovorin) regimens, tegafur/uracil + calcium folinate has similar efficacy with less toxicity and is more convenient because it is an oral regimen. Early studies have also shown potential cost savings because of fewer complications.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials as Topic
  • Colorectal Neoplasms / drug therapy*
  • Drug Combinations
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacokinetics*
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / pharmacokinetics
  • Tegafur / administration & dosage
  • Tegafur / pharmacokinetics
  • Uracil / administration & dosage
  • Uracil / pharmacokinetics

Substances

  • Drug Combinations
  • UFT(R) drug
  • Tegafur
  • Uracil
  • Leucovorin
  • Fluorouracil