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Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe

Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are, however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropyrimidine dosing based on...

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Autores principales: Afolabi, Boluwatife Lawrence, Mazhindu, Tinashe, Zedias, Chikwambi, Borok, Margaret, Ndlovu, Ntokozo, Masimirembwa, Collen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141018/
https://www.ncbi.nlm.nih.gov/pubmed/37108974
http://dx.doi.org/10.3390/jpm13040588
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author Afolabi, Boluwatife Lawrence
Mazhindu, Tinashe
Zedias, Chikwambi
Borok, Margaret
Ndlovu, Ntokozo
Masimirembwa, Collen
author_facet Afolabi, Boluwatife Lawrence
Mazhindu, Tinashe
Zedias, Chikwambi
Borok, Margaret
Ndlovu, Ntokozo
Masimirembwa, Collen
author_sort Afolabi, Boluwatife Lawrence
collection PubMed
description Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are, however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropyrimidine dosing based on dihydropyrimidine dehydrogenase (DPYD) genetic polymorphism and have been shown to reduce these AEs in patients of European ancestry. This study aimed to evaluate, for the first time, the clinical applicability of these guidelines in a cohort of cancer patients on fluoropyrimidine standard of care treatment in Zimbabwe. DNA was extracted from whole blood and used for DPYD genotyping. Adverse events were monitored for six months using the Common Terminology Criteria for AEs (CTCAE) v.5.0. None of the 150 genotyped patients was a carrier of any of the pathogenic variants (DPYD*2A, DPYD*13, rs67376798, or rs75017182). However, severe AEs were high (36%) compared to those reported in the literature from other populations. There was a statistically significant association between BSA (p = 0.0074) and BMI (p = 0.0001) with severe global AEs. This study has shown the absence of the currently known actionable DPYD variants in the Zimbabwean cancer patient cohort. Therefore, the current pathogenic variants in the guidelines might not be feasible for all populations hence the call for modification of the current DPYD guidelines to include minority populations for the benefit of all diverse patients.
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spelling pubmed-101410182023-04-29 Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe Afolabi, Boluwatife Lawrence Mazhindu, Tinashe Zedias, Chikwambi Borok, Margaret Ndlovu, Ntokozo Masimirembwa, Collen J Pers Med Communication Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are, however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropyrimidine dosing based on dihydropyrimidine dehydrogenase (DPYD) genetic polymorphism and have been shown to reduce these AEs in patients of European ancestry. This study aimed to evaluate, for the first time, the clinical applicability of these guidelines in a cohort of cancer patients on fluoropyrimidine standard of care treatment in Zimbabwe. DNA was extracted from whole blood and used for DPYD genotyping. Adverse events were monitored for six months using the Common Terminology Criteria for AEs (CTCAE) v.5.0. None of the 150 genotyped patients was a carrier of any of the pathogenic variants (DPYD*2A, DPYD*13, rs67376798, or rs75017182). However, severe AEs were high (36%) compared to those reported in the literature from other populations. There was a statistically significant association between BSA (p = 0.0074) and BMI (p = 0.0001) with severe global AEs. This study has shown the absence of the currently known actionable DPYD variants in the Zimbabwean cancer patient cohort. Therefore, the current pathogenic variants in the guidelines might not be feasible for all populations hence the call for modification of the current DPYD guidelines to include minority populations for the benefit of all diverse patients. MDPI 2023-03-28 /pmc/articles/PMC10141018/ /pubmed/37108974 http://dx.doi.org/10.3390/jpm13040588 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Afolabi, Boluwatife Lawrence
Mazhindu, Tinashe
Zedias, Chikwambi
Borok, Margaret
Ndlovu, Ntokozo
Masimirembwa, Collen
Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe
title Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe
title_full Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe
title_fullStr Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe
title_full_unstemmed Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe
title_short Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe
title_sort pharmacogenetics and adverse events in the use of fluoropyrimidine in a cohort of cancer patients on standard of care treatment in zimbabwe
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141018/
https://www.ncbi.nlm.nih.gov/pubmed/37108974
http://dx.doi.org/10.3390/jpm13040588
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