Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity

Wen Wee Ma, Muhammad Wasif Saif, Bassel F. El-Rayes, Marwan G. Fakih, Thomas H. Cartwright, James A. Posey, Thomas R. King, Reid W. von Borstel, Michael K. Bamat

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

BACKGROUND: Increased susceptibility to 5-fluorouracil (5-FU)/capecitabine can lead to rapidly occurring toxicity caused by impaired clearance, dihydropyrimidine dehydrogenase deficiency, and other genetic variations in the enzymes that metabolize 5-FU. Life-threatening 5-FU overdoses occur because of infusion pump errors, dosage miscalculations, and accidental or suicidal ingestion of capecitabine. Uridine triacetate (Vistogard) was approved in 2015 for adult and pediatric patients who exhibit early-onset severe or life-threatening 5-FU/capecitabine toxicities or present with an overdose. Uridine triacetate delivers high concentrations of uridine, which competes with toxic 5-FU metabolites. METHODS: In 2 open-label clinical studies, patients who presented with a 5-FU/capecitabine overdose or an early onset of severe toxicities were treated. Patients received uridine triacetate as soon as possible (most within the first 96 hours after 5-FU/capecitabine). Outcomes included survival, resumption of chemotherapy, and safety. Their survival was compared with the survival of a historical cohort of overdose patients who received only supportive care. RESULTS: A total of 137 of 142 overdose patients (96%) treated with uridine triacetate survived and had a rapid reversal of severe acute cardiotoxicity and neurotoxicity; in addition, mucositis and leukopenia were prevented, or the patients recovered from them. In the historical cohort, 21 of 25 patients (84%) died. Among the 141 uridine triacetate–treated overdose patients with a diagnosis of cancer (the noncancer patients included 6 intentional or accidental pediatric overdoses), 53 resumed chemotherapy in < 30 days (median time after 5-FU, 19.6 days), and this indicated a rapid recovery from toxicity. Adverse reactions in patients receiving uridine triacetate included vomiting (8.1%), nausea (4.6%), and diarrhea (3.5%). CONCLUSIONS: In these studies, uridine triacetate was a safe and effective lifesaving antidote for capecitabine and 5-FU overexposure, and it facilitated the rapid resumption of chemotherapy. Cancer 2017;123:345–356.

Original languageEnglish (US)
Pages (from-to)345-356
Number of pages12
JournalCancer
Volume123
Issue number2
DOIs
StatePublished - Jan 1 2017

Keywords

  • 5-fluorouracil
  • capecitabine
  • fluoropyrimidines
  • overdose
  • toxicity
  • uracil

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ma, W. W., Saif, M. W., El-Rayes, B. F., Fakih, M. G., Cartwright, T. H., Posey, J. A., King, T. R., von Borstel, R. W., & Bamat, M. K. (2017). Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity. Cancer, 123(2), 345-356. https://doi.org/10.1002/cncr.30321