Cargando…

Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma

Pharmacogenomic testing may have clinical value in the treatment of patients with gastrointestinal malignancies such as colorectal and pancreatic cancer. These types of cancer are often treated with combination chemotherapy regimens. These regimens can lead to severe adverse effects in patients with...

Descripción completa

Detalles Bibliográficos
Autores principales: Velez-Velez, Lisa M., Hughes, Caren L., Kasi, Pashtoon Murtaza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249237/
https://www.ncbi.nlm.nih.gov/pubmed/30498448
http://dx.doi.org/10.3389/fphar.2018.01309
_version_ 1783372701576986624
author Velez-Velez, Lisa M.
Hughes, Caren L.
Kasi, Pashtoon Murtaza
author_facet Velez-Velez, Lisa M.
Hughes, Caren L.
Kasi, Pashtoon Murtaza
author_sort Velez-Velez, Lisa M.
collection PubMed
description Pharmacogenomic testing may have clinical value in the treatment of patients with gastrointestinal malignancies such as colorectal and pancreatic cancer. These types of cancer are often treated with combination chemotherapy regimens. These regimens can lead to severe adverse effects in patients with diminished drug tolerability potentially due to certain genetic variants in the enzymes involved in the metabolism of the chemotherapies. Genetic variants resulting in decreased enzymatic activity of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and dihydropyrimidine dehydrogenase (DPD) are known to increase irinotecan and 5-fluorouracil-related toxicity, respectively. We report a case of a patient with pancreatic adenocarcinoma who was found to be not only homozygous for the UGT1A1(∗)28 allele, but also heterozygous for a DPYD variant through pharmacogenomic testing. Potentially severe adverse effects were prevented in this patient’s case by implementing preemptive dose reductions. On the basis of the significant implications of chemotherapy-related toxicity in this and other similar cases, we report on the clinical value of integrating pharmacogenomic testing into clinical practice to allow for preemptive and/or point-of-care dose reductions in patients potentially at risk for increased toxicity. This is even more important in an era where combinatorial triplet chemotherapies are increasingly being used.
format Online
Article
Text
id pubmed-6249237
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-62492372018-11-29 Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma Velez-Velez, Lisa M. Hughes, Caren L. Kasi, Pashtoon Murtaza Front Pharmacol Pharmacology Pharmacogenomic testing may have clinical value in the treatment of patients with gastrointestinal malignancies such as colorectal and pancreatic cancer. These types of cancer are often treated with combination chemotherapy regimens. These regimens can lead to severe adverse effects in patients with diminished drug tolerability potentially due to certain genetic variants in the enzymes involved in the metabolism of the chemotherapies. Genetic variants resulting in decreased enzymatic activity of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and dihydropyrimidine dehydrogenase (DPD) are known to increase irinotecan and 5-fluorouracil-related toxicity, respectively. We report a case of a patient with pancreatic adenocarcinoma who was found to be not only homozygous for the UGT1A1(∗)28 allele, but also heterozygous for a DPYD variant through pharmacogenomic testing. Potentially severe adverse effects were prevented in this patient’s case by implementing preemptive dose reductions. On the basis of the significant implications of chemotherapy-related toxicity in this and other similar cases, we report on the clinical value of integrating pharmacogenomic testing into clinical practice to allow for preemptive and/or point-of-care dose reductions in patients potentially at risk for increased toxicity. This is even more important in an era where combinatorial triplet chemotherapies are increasingly being used. Frontiers Media S.A. 2018-11-15 /pmc/articles/PMC6249237/ /pubmed/30498448 http://dx.doi.org/10.3389/fphar.2018.01309 Text en Copyright © 2018 Velez-Velez, Hughes and Kasi. http://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
Velez-Velez, Lisa M.
Hughes, Caren L.
Kasi, Pashtoon Murtaza
Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma
title Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma
title_full Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma
title_fullStr Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma
title_full_unstemmed Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma
title_short Clinical Value of Pharmacogenomic Testing in a Patient Receiving FOLFIRINOX for Pancreatic Adenocarcinoma
title_sort clinical value of pharmacogenomic testing in a patient receiving folfirinox for pancreatic adenocarcinoma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249237/
https://www.ncbi.nlm.nih.gov/pubmed/30498448
http://dx.doi.org/10.3389/fphar.2018.01309
work_keys_str_mv AT velezvelezlisam clinicalvalueofpharmacogenomictestinginapatientreceivingfolfirinoxforpancreaticadenocarcinoma
AT hughescarenl clinicalvalueofpharmacogenomictestinginapatientreceivingfolfirinoxforpancreaticadenocarcinoma
AT kasipashtoonmurtaza clinicalvalueofpharmacogenomictestinginapatientreceivingfolfirinoxforpancreaticadenocarcinoma