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Oral Capecitabine Exposures and Use of Uridine Triacetate: A 20-Year Retrospective Analysis

BACKGROUND AND OBJECTIVES: Capecitabine is an oral prodrug of 5-fluorouracil. Toxicity can occur during therapy as well as acutely with overdose and particular genetic susceptibilities. Uridine triacetate is an effective antidote if given within 96 h of exposure. This study seeks to characterize acc...

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Detalles Bibliográficos
Autores principales: Seltzer, Justin A., Friedman, Nathan A., Hardin, Jeremy, Galust, Henrik, Cantrell, F. Lee, Minns, Alicia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198921/
https://www.ncbi.nlm.nih.gov/pubmed/37072662
http://dx.doi.org/10.1007/s40261-023-01268-5
Descripción
Sumario:BACKGROUND AND OBJECTIVES: Capecitabine is an oral prodrug of 5-fluorouracil. Toxicity can occur during therapy as well as acutely with overdose and particular genetic susceptibilities. Uridine triacetate is an effective antidote if given within 96 h of exposure. This study seeks to characterize accidental and intentional capecitabine exposures and uridine triacetate use, about which little has been published. METHODS: A retrospective review of capecitabine exposures from 30 April 2001 to 31 December 2021 reported to a statewide poison control center was performed. All single-substance oral exposures were included. RESULTS: In total, 81 of 128 reviewed cases were included, with a median age of 63 years. In total, 49 were acute-on-chronic exposures and 32 were acute exposures in capecitabine-naïve patients, 29 of which were accidental. Fifty-six (69%) were managed at home. Of these, none later recontacted the poison control center to report symptoms or were known to have later had healthcare facility evaluations. Of the 25 cases presenting for healthcare facility evaluation, 4 were acutely symptomatic. Thirteen were eligible for uridine triacetate, and six received it; no new or progressive toxicity was reported after. Three developed mild latent toxicity; otherwise, no morbidity or mortality was reported. CONCLUSIONS: Accidental acute-on-chronic and acute ingestions of capecitabine appear to be well tolerated; most cases were managed at home. Unfortunately, little is known regarding the threshold at which toxicity may present following exposures. The threshold may vary individually given genetic susceptibilities. Management was heterogeneous, likely reflecting inadequate guidelines. Further research is needed to better delineate at-risk populations and treatment strategies.