Early-Onset 5-Fluorouracil Toxicity in a Patient Negative for Dihydropyrimidine Dehydrogenase Mutations: The Clinical Course of Reversal with Uridine Triacetate

Pharmacotherapy. 2016 Nov;36(11):e178-e182. doi: 10.1002/phar.1841. Epub 2016 Nov 4.

Abstract

An antimetabolite pyridine analog, 5-fluorouracil (5-FU), is used to treat solid tumors. Early toxicities may occur at standard doses of 5-FU due to dihydropyrimidine dehydrogenase (DPD) deficiency. Uridine triacetate, approved by the Food and Drug Administration in 2015, is an oral prodrug of uridine, a pharmacologic antidote for 5-FU toxicity. To our knowledge, this is the first case report that documents the clinical course of a patient treated with uridine triacetate to reverse early-onset 5-FU toxicity negative for DPD mutations. We describe the case of a 73-year-old man with anal cancer treated with standard-of-care chemotherapy and radiation. Two days after completion of his initial 5-FU infusion, the patient developed severe mucositis and extreme fatigue, followed by a rapid decline in his blood cell counts and fevers. The patient was initiated on uridine triacetate 86 hours after completion of his 5-FU infusion. Over a 10-day hospital length of stay, the patient's absolute neutrophil count recovered to within normal limits, and his mucositis significantly improved. At follow-up visits, the patient denied any residual symptoms of 5-FU toxicity. We describe the patient's clinical course from hospital presentation to 31 days after initiation of uridine triacetate.

Keywords: 5-fluorouracil; adverse drug reaction; early-onset toxicity; uridine triacetate.

Publication types

  • Case Reports

MeSH terms

  • Acetates / therapeutic use*
  • Aged
  • Antidotes / therapeutic use
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Anus Neoplasms / drug therapy*
  • Anus Neoplasms / genetics
  • Dihydrouracil Dehydrogenase (NADP) / genetics
  • Fatigue / chemically induced
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects*
  • Follow-Up Studies
  • Humans
  • Male
  • Mucositis / chemically induced
  • Mucositis / drug therapy
  • Mutation
  • Neutrophils / metabolism
  • Time Factors
  • Uridine / analogs & derivatives*
  • Uridine / therapeutic use

Substances

  • Acetates
  • Antidotes
  • Antimetabolites, Antineoplastic
  • uridine triacetate
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil
  • Uridine