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Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil

5-fluorouracil (5-FU) and its pro-drug capecitabine are widely used anticancer agents. Most 5-FU catabolism is dependent on dihydropyrimidine dehydrogenase (DPD) encoded by the DPYD gene, and DPYD variants that reduce DPD function increase 5-FU toxicity. Most DPD deficient patients are heterozygous...

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Autores principales: Winquist, Lauren E., Sanatani, Michael, Kim, Richard B., Winquist, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816174/
https://www.ncbi.nlm.nih.gov/pubmed/33704179
http://dx.doi.org/10.3390/curroncol28010012
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author Winquist, Lauren E.
Sanatani, Michael
Kim, Richard B.
Winquist, Eric
author_facet Winquist, Lauren E.
Sanatani, Michael
Kim, Richard B.
Winquist, Eric
author_sort Winquist, Lauren E.
collection PubMed
description 5-fluorouracil (5-FU) and its pro-drug capecitabine are widely used anticancer agents. Most 5-FU catabolism is dependent on dihydropyrimidine dehydrogenase (DPD) encoded by the DPYD gene, and DPYD variants that reduce DPD function increase 5-FU toxicity. Most DPD deficient patients are heterozygous and can be treated with reduced 5-FU dosing. We describe a patient with a genotype associated with near complete absence of DPD function, and severe and likely fatal toxicity with 5-FU treatment. The patient was treated effectively with alternative systemic therapy. Routine pretreatment DPYD genotyping is recommended by the European Medicines Agency, and guidelines for use of 5-FU in DPD deficient patients are available. However, outside the province of Quebec, routine pretreatment screening for DPD deficiency remains unavailable in Canada. It is likely our patient would have died from 5-FU toxicity under the current standard of care, but instead provides an example of the potential benefit of DPYD screening on patient outcomes.
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spelling pubmed-78161742021-01-27 Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil Winquist, Lauren E. Sanatani, Michael Kim, Richard B. Winquist, Eric Curr Oncol Case Report 5-fluorouracil (5-FU) and its pro-drug capecitabine are widely used anticancer agents. Most 5-FU catabolism is dependent on dihydropyrimidine dehydrogenase (DPD) encoded by the DPYD gene, and DPYD variants that reduce DPD function increase 5-FU toxicity. Most DPD deficient patients are heterozygous and can be treated with reduced 5-FU dosing. We describe a patient with a genotype associated with near complete absence of DPD function, and severe and likely fatal toxicity with 5-FU treatment. The patient was treated effectively with alternative systemic therapy. Routine pretreatment DPYD genotyping is recommended by the European Medicines Agency, and guidelines for use of 5-FU in DPD deficient patients are available. However, outside the province of Quebec, routine pretreatment screening for DPD deficiency remains unavailable in Canada. It is likely our patient would have died from 5-FU toxicity under the current standard of care, but instead provides an example of the potential benefit of DPYD screening on patient outcomes. MDPI 2020-12-18 /pmc/articles/PMC7816174/ /pubmed/33704179 http://dx.doi.org/10.3390/curroncol28010012 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Winquist, Lauren E.
Sanatani, Michael
Kim, Richard B.
Winquist, Eric
Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil
title Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil
title_full Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil
title_fullStr Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil
title_full_unstemmed Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil
title_short Near Miss or Standard of Care? DPYD Screening for Cancer Patients Receiving Fluorouracil
title_sort near miss or standard of care? dpyd screening for cancer patients receiving fluorouracil
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816174/
https://www.ncbi.nlm.nih.gov/pubmed/33704179
http://dx.doi.org/10.3390/curroncol28010012
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