Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper

Oncol Res Treat. 2020;43(11):628-636. doi: 10.1159/000510258. Epub 2020 Oct 23.

Abstract

Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%.

Summary: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.

Keywords: 5-Fluorouacil; Capecitabine; Dihydropyrimidine dehydrogenase mutation; Genetic testing; Tegafur.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Austria
  • Capecitabine / administration & dosage
  • Capecitabine / adverse effects
  • Consensus
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / adverse effects
  • Genetic Testing / methods*
  • Genetic Testing / standards
  • Genotype
  • Germany
  • Humans
  • Male
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Phenotype
  • Practice Guidelines as Topic
  • Switzerland
  • Tegafur / administration & dosage
  • Tegafur / adverse effects

Substances

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