Dihydropyrimidine Dehydrogenase Deficiency and Implementation of Upfront DPYD Genotyping.
Cassandra WhiteRodney J ScottChristine PaulAndrew ZiolkowskiDavid MossmanStephen B FoxMichael MichaelStephen P AcklandPublished in: Clinical pharmacology and therapeutics (2022)
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.
Keyphrases
- healthcare
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- genome wide
- primary care
- high throughput
- emergency department
- prognostic factors
- type diabetes
- clinical trial
- oxidative stress
- gene expression
- patient reported outcomes
- early onset
- radiation therapy
- transcription factor
- copy number
- open label
- insulin resistance
- childhood cancer
- high density
- genome wide analysis