Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil

Curr Oncol. 2020 Dec 18;28(1):94-97. doi: 10.3390/curroncol28010012.

Abstract

5-fluorouracil (5-FU) and its pro-drug capecitabine are widely used anticancer agents. Most 5-FU catabolism is dependent on dihydropyrimidine dehydrogenase (DPD) encoded by the DPYD gene, and DPYD variants that reduce DPD function increase 5-FU toxicity. Most DPD deficient patients are heterozygous and can be treated with reduced 5-FU dosing. We describe a patient with a genotype associated with near complete absence of DPD function, and severe and likely fatal toxicity with 5-FU treatment. The patient was treated effectively with alternative systemic therapy. Routine pretreatment DPYD genotyping is recommended by the European Medicines Agency, and guidelines for use of 5-FU in DPD deficient patients are available. However, outside the province of Quebec, routine pretreatment screening for DPD deficiency remains unavailable in Canada. It is likely our patient would have died from 5-FU toxicity under the current standard of care, but instead provides an example of the potential benefit of DPYD screening on patient outcomes.

Keywords: adverse effects; cancer; dihydropyrimidine dehydrogenase; drug therapy; fluoropyrimidines; single nucleotide polymorphisms.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects
  • Dihydrouracil Dehydrogenase (NADP) / genetics
  • Early Detection of Cancer
  • Fluorouracil / adverse effects
  • Humans
  • Near Miss, Healthcare*
  • Neoplasms* / drug therapy
  • Standard of Care

Substances

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