Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity

Br J Clin Pharmacol. 2007 Aug;64(2):237-40. doi: 10.1111/j.1365-2125.2007.02869.x. Epub 2007 Mar 1.

Abstract

Aims: To examine retrospectively the relationship between DPD phenotype/genotype and the intensity of 5FU toxicity.

Methods: One hundred and thirty-one case-reports (81 women, 50 men) with 5FU-related toxicity were analyzed.

Results: The lower the DPD activity (10-504 pmol min(-1) mg(-1)), the higher the toxicity grade was scored (P < 0.01). Toxicity-related deaths occurred in nine patients (eight women) who significantly expressed lower DPD activity than other patients. Two of the deceased patients had normal DPD activity. The IVS14+1G>A mutation, analyzed in 93 patients, was detected in two patients (nonlethal toxicity).

Conclusions: The IVS14+1G>A mutation may not help prevent toxicity and patients with normal DPD activity may develop life-threatening 5FU toxicity.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Dihydrouracil Dehydrogenase (NADP) / administration & dosage*
  • Dihydrouracil Dehydrogenase (NADP) / adverse effects
  • Female
  • Fluorouracil / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense / drug effects*
  • Polymorphism, Genetic

Substances

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