Fluoropyrimidine-Associated Toxicity in Two Gastrointestinal Cancer Patients: Potential Role of Common DPYD Polymorphisms

Chemotherapy. 2017;62(5):323-326. doi: 10.1159/000477333. Epub 2017 Jun 15.

Abstract

While the majority of patients can be treated safely with fluoropyrimidine, some experience severe fluoropyrimidine-associated toxicity. The frequency and severity of these adverse events vary from patient to patient and are partially explained by genetic polymorphism into the dihydropyrimidine dehydrogenase (DPYD) gene. Carriers of the rare allelic variants DPYD*2A, DPYD*13, and DPYD D949V are more likely to experience severe adverse reactions during fluoropyrimidine-based therapy. However, these 3 genetic variants explain only a small percentage of the overall drug toxicity, and more frequent ones such as homozygous or compound heterozygous DPYD V732I can play a key role.

Keywords: DPYD; Fluoropyrimidine; Toxicity; V732I.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / pathology
  • Gene Frequency
  • Genotype
  • Heterozygote
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Nausea / etiology
  • Organoplatinum Compounds / therapeutic use
  • Polymorphism, Genetic
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects*
  • Stomatitis / etiology

Substances

  • Organoplatinum Compounds
  • Pyrimidines
  • Dihydrouracil Dehydrogenase (NADP)
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol