Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA?

J Oncol Pharm Pract. 2020 Apr;26(3):747-753. doi: 10.1177/1078155219865597. Epub 2019 Aug 5.

Abstract

Fluoropyrimidine-based regimens are among the most commonly used chemotherapy combinations for the treatment of solid tumors. Several genetic polymorphisms that are implicated with fluoropyrimidine anabolism and catabolism have been associated with the development of life-threatening toxicities. Uridine triacetate is an FDA-approved antidote for 5-fluorouracil or capecitabine overdose and early-onset, life-threatening toxicity within 96 h of last chemotherapy dose. To date, it is not accessible for Greek patients as per the current summary of product characteristic's time restrictions. We report and discuss the course and outcome of capecitabine toxicity in a 66-year-old female colorectal cancer patient with heterozygous dihydropyrimidine dehydrogenase deficiency. This paper highlights the difficulty in timely access of this lifesaving medication for Greek and possibly other European patients.

Keywords: Cardiotoxicity; dihydropyrimidine dehydrogenase deficiency; early-onset capecitabine toxicity; uridine triacetate indications.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Acetates / administration & dosage*
  • Aged
  • Antidotes / therapeutic use
  • Antimetabolites, Antineoplastic / administration & dosage
  • Capecitabine / administration & dosage
  • Capecitabine / adverse effects*
  • Dihydropyrimidine Dehydrogenase Deficiency / complications*
  • Female
  • Humans
  • Neoplasms / drug therapy
  • Uridine / administration & dosage
  • Uridine / analogs & derivatives*

Substances

  • Acetates
  • Antidotes
  • Antimetabolites, Antineoplastic
  • uridine triacetate
  • Capecitabine
  • Uridine