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Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature

5-fluorouracil (5FU) and capecitabine are fluoropyrimidine anti-neoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimdine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA...

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Autores principales: Jacob, Aasems, Sekkath Veedu, Janeesh, Selene, Insija, Raj, Rishi, Kannan, Lakshmi, Patel, Reema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490183/
https://www.ncbi.nlm.nih.gov/pubmed/36160401
http://dx.doi.org/10.3389/fphar.2022.977734
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author Jacob, Aasems
Sekkath Veedu, Janeesh
Selene, Insija
Raj, Rishi
Kannan, Lakshmi
Patel, Reema
author_facet Jacob, Aasems
Sekkath Veedu, Janeesh
Selene, Insija
Raj, Rishi
Kannan, Lakshmi
Patel, Reema
author_sort Jacob, Aasems
collection PubMed
description 5-fluorouracil (5FU) and capecitabine are fluoropyrimidine anti-neoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimdine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA) is an emergency treatment for overdoses and early onset, severe or life-threatening toxicities from fluoropyrimidines. It is approved for use in adults and children within 96 h of last fluoropyrimidine administration. We present the case of a 64-year-old male treated with 5-FU and oxaliplatin as adjuvant systemic therapy for stage IIIA rectal cancer who developed delayed central nervous system toxicity 18 days after initiating chemotherapy. He had rapidly worsening encephalopathy and ataxia. Laboratory workups, MRI brain and EEG were negative. He was started on UTA with concerns of 5-FU toxicity due to the life-threatening nature of his condition even beyond the recommended 96-h time cut-off. He had rapid improvement in clinical status and resolution of encephalopathy. DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. This report demonstrates the importance of identifying delayed side effects with fluoropyrimidine therapy and potential treatment for reversing these effects. We also did an extensive literature review and obtained reports from the uridine triacetate clinical trials on patients receiving UTA after the 96-h cut-off. Based on our experience and previous published reports, a patient developing life-threatening delayed 5-FU toxicity should also be considered for UTA on a case-by-case basis.
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spelling pubmed-94901832022-09-22 Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature Jacob, Aasems Sekkath Veedu, Janeesh Selene, Insija Raj, Rishi Kannan, Lakshmi Patel, Reema Front Pharmacol Pharmacology 5-fluorouracil (5FU) and capecitabine are fluoropyrimidine anti-neoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimdine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA) is an emergency treatment for overdoses and early onset, severe or life-threatening toxicities from fluoropyrimidines. It is approved for use in adults and children within 96 h of last fluoropyrimidine administration. We present the case of a 64-year-old male treated with 5-FU and oxaliplatin as adjuvant systemic therapy for stage IIIA rectal cancer who developed delayed central nervous system toxicity 18 days after initiating chemotherapy. He had rapidly worsening encephalopathy and ataxia. Laboratory workups, MRI brain and EEG were negative. He was started on UTA with concerns of 5-FU toxicity due to the life-threatening nature of his condition even beyond the recommended 96-h time cut-off. He had rapid improvement in clinical status and resolution of encephalopathy. DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. This report demonstrates the importance of identifying delayed side effects with fluoropyrimidine therapy and potential treatment for reversing these effects. We also did an extensive literature review and obtained reports from the uridine triacetate clinical trials on patients receiving UTA after the 96-h cut-off. Based on our experience and previous published reports, a patient developing life-threatening delayed 5-FU toxicity should also be considered for UTA on a case-by-case basis. Frontiers Media S.A. 2022-09-07 /pmc/articles/PMC9490183/ /pubmed/36160401 http://dx.doi.org/10.3389/fphar.2022.977734 Text en Copyright © 2022 Jacob, Sekkath Veedu, Selene, Raj, Kannan and Patel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Jacob, Aasems
Sekkath Veedu, Janeesh
Selene, Insija
Raj, Rishi
Kannan, Lakshmi
Patel, Reema
Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature
title Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature
title_full Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature
title_fullStr Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature
title_full_unstemmed Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature
title_short Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature
title_sort case report: uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: a case report and review of literature
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490183/
https://www.ncbi.nlm.nih.gov/pubmed/36160401
http://dx.doi.org/10.3389/fphar.2022.977734
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