Pyrimidine Degradation Defects and Severe 5-fluorouracil Toxicity

Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1371-5. doi: 10.1081/NCN-200027624.

Abstract

5-Fluorouracil (5FU) remains one of the most frequently prescribed chemotherapeutic drugs for the treatment of cancer. Recently, the pivotal role of the catabolic pathway of 5FU in the determination of toxicity towards 5FU has been highlighted. Patients with a (partial) dihydropyrimidine dehydrogenase deficiency proved to be at risk of developing severe toxicity after the administration of 5FU. A partial dihydropyrimidinase deficiency proved to be a novel pharmacogenetic disorder associated with severe 5FU toxicity.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Dihydropyrimidine Dehydrogenase Deficiency
  • Dihydrouracil Dehydrogenase (NADP) / genetics
  • Exons
  • Fluorouracil / toxicity*
  • Genome
  • Humans
  • Models, Chemical
  • Models, Genetic
  • Pyrimidines / chemistry*

Substances

  • Antimetabolites, Antineoplastic
  • Pyrimidines
  • Dihydrouracil Dehydrogenase (NADP)
  • pyrimidine
  • Fluorouracil