[Detection of dihydropyrimidine dehydrogenase deficiency before treatment by fluoropyrimidines]

Therapie. Mar-Apr 2007;62(2):99-103. doi: 10.2515/therapie:2007023. Epub 2007 Jun 21.
[Article in French]

Abstract

Numerous toxic side-effects, sometimes severe, are regularly reported in patients treated with 5-fluorouracil, and oral fluoropyrimidines, UFT and capecitabine, in metastatic and adjuvant setting. These toxic effects are due to a large interindividual variability of the metabolism, mainly depending on dihydropyrimidine dehydrogenase activity (DPD), the major enzyme of the catabolism of fluoropyrimidines. Thus, the patients with a DPD deficiency are at high risk of early severe acute toxicity, with this kind of drug. These toxic side-effects are potentially lethal. DPD deficiency frequencies, partial or complete, are about 3-5% and 0.2% respectively. They are most often due to a gene polymorphism. Different techniques for the detection of DPD deficiency before treatment have been reported: phenotypic, such as the plasma ratio of dihydrouracil/uracil, or genotypic, such as the detection of DPD gene variants, deleterious for enzyme activity. The pretherapeutic detection of DPD deficiency would permit to avoid almost every early acute toxic side-effects. We must emphasize that it is not merely a genetic result, since the detection of a deficiency most often does not contra-indicate the use of a fluoropyrimidine, but it must be combined with therapeutic advice.

Publication types

  • English Abstract

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Capecitabine
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Dihydropyrimidine Dehydrogenase Deficiency*
  • Dihydrouracil Dehydrogenase (NADP) / genetics
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Tegafur / adverse effects
  • Uracil / adverse effects

Substances

  • Antineoplastic Agents
  • Deoxycytidine
  • Tegafur
  • Uracil
  • Capecitabine
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil

Supplementary concepts

  • 1-UFT protocol