Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency

Abstract

Fluoropyrimidine drugs (FP) are the backbone of many chemotherapy protocols for treating solid tumours. The rate-limiting step of fluoropyrimidine catabolism is dihydropyrimidine dehydrogenase (DPD), and deficiency in DPD activity can result in severe and even fatal toxicity. In this review, we survey the evidence-based pharmacogenetics and therapeutic recommendations regarding DPYD (the gene encoding DPD) genotyping and DPD phenotyping to prevent toxicity and optimize dosing adaptation before FP administration. The French experience of mandatory DPD-deficiency screening prior to initiating FP is discussed.

Keywords: 5-Fluorouracile; DPD; DPYD; Dihydropyrimidine dehydrogenase; Drug toxicity; Fluoropyrimidine; Genotyping; Guidelines; Pharmacogenetics; Phenotyping.