DPYD Genotyping Before Fluoropyrimidine Chemotherapy: Clinical Evidence Supports Upfront Testing
This review presents the clinical and cost-effectiveness evidence for pretreatment DPYD genotyping to identify patients at risk of severe fluoropyrimidine toxicity due to dihydropyrimidine dehydrogenase deficiency. Recently endorsed by multiple European countries and the UK, upfront testing with prospective dose reduction has been shown to reduce morbidity without compromising efficacy. The paper provides a practical implementation roadmap for laboratories establishing DPYD genotyping services.
The original study
Dihydropyrimidine Dehydrogenase Deficiency and Implementation of Upfront DPYD Genotyping.
- Authors
- White C, Scott RJ, Paul C, Ziolkowski A, Mossman D, Fox SB, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Review
- PMID
- 35607723
Original abstract
Fluoropyrimidines (FP; 5-fluorouracil, capecitabine, and tegafur) are a commonly prescribed class of antimetabolite chemotherapies, used for various solid organ malignancies in over 2 million patients globally per annum. Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is the critical enzyme implicated in FP metabolism. DPYD variant genotypes can result in decreased DPD production, leading to the development of severe toxicities resulting in hospitalization, intensive care admission, and even death. Management of toxicity incurs financial burden on both patients and healthcare systems alike. Upfront DPYD genotyping to identify variant carriers allows an opportunity to identify patients who are at high risk to suffer from serious toxicities and allow prospective dose adjustment of FP treatment. This approach has been shown to reduce patient morbidity, as well as improve the cost-effectiveness of managing FP treatment. Upfront DPYD genotyping has been recently endorsed by several countries in Europe and the United Kingdom. This review summarizes current knowledge about DPD deficiency and upfront DPYD genotyping, including clinical and cost-effectiveness outcomes, with the intent of supporting implementation of an upfront DPYD genotyping service with individualized dose-personalization.