Near Miss or Standard of Care? <i>DPYD</i> Screening for Cancer Patients Receiving Fluorouracil

• Main Authors: Lauren E. Winquist, Michael Sanatani, Richard B. Kim, Eric Winquist
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: Current Oncology
• Subjects: fluoropyrimidines; dihydropyrimidine dehydrogenase; cancer; adverse effects; single nucleotide polymorphisms; drug therapy
• Online Access: https://www.mdpi.com/1718-7729/28/1/12
• ISSN: 1198-0052; 1718-7729

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 <i>DPYD</i> gene, and <i>DPYD</i> 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 <i>DPYD</i> 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 <i>DPYD</i> screening on patient outcomes.