Can dihydropyrimidine dehydrogenase impact 5-fluorouracil-based treatment?

Eur J Cancer. 2000 Jan;36(1):37-42. doi: 10.1016/s0959-8049(99)00211-7.

Abstract

More than 80% of an administered 5-fluorouracil (5-FU) dose is degraded by dihydropyrimidine dehydrogenase (DPD), making it an important regulator of this commonly used anticancer agent. The high variation in population DPD activity, association with 5-FU activity, and development of DPD inhibitors have all contributed to the current focus on this enzyme. This review details the impact of DPD on 5-FU pharmacology, catalogues recent information on DPD mutations, evaluates the case for tumour DPD as a source of 5-FU resistance and introduces the clinical case for DPD inhibitors as a mechanism for the use of oral fluoropyrimidine therapies.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Circadian Rhythm
  • Dihydrouracil Dehydrogenase (NADP)
  • Drug Interactions
  • Female
  • Fluorouracil / metabolism
  • Fluorouracil / therapeutic use*
  • Humans
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oxidoreductases / metabolism
  • Oxidoreductases / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil