Benefit of uridine triacetate (Vistogard) in rescuing severe 5-fluorouracil toxicity in patients with dihydropyrimidine dehydrogenase (DPYD) deficiency

摘要

5-Fluorouracil (5-FU), an analog of uracil, is one of the most commonly used chemotherapeutic agents and like other agents has a narrow therapeutic index limited by toxicity. Compared to previous attempts, uridine triacetate (Vistogard) has shown to increase the potential efficacy of 5-FU by allowing administering a higher dose and decreasing the toxicity. Recently, Vistogard received orphan drug designation from the FDA as an antidote in the treatment of 5-FU poisoning and from the European Medicines Agency as a treatment for 5-FU overdose. However, no data have been published to date in humans who were rescued by this agent following severe toxicity associated with 5-FU due to dihydropyrimidine dehydrogenase (DPYD) deficiency, the enzyme which is responsible for the elimination of approximately 80 % of the administered dose of 5-FU.