Lethal outcome of 5-fluorouracil infusion in a patient with a total DPD deficiency and a double DPYD and UTG1A1 gene mutation.

摘要

5-Fluorouracil (5-FU)-based chemotherapy has been widely used for almost 50 years in the treatment of solid malignancies, especially in digestive cancers. Its main effect consists in the inhibition, via its active metabolite, of thymidylate synthase, a major enzyme involved in DNA synthesis. In normal conditions, less than 20% of the administered 5-FU is used in this anabolic pathway while more than 80% is catabolized via dihydropyrimidine dehydrogenase (DPD) [1]. This is the initial and rate-limiting enzyme in the catabolic pathway and therefore a partial or complete DPD deficiency is associated with different degrees of 5-FU toxicity whose most frequent manifestations include neutropenia, mucositis and diarrhoea [2].