Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study
Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the *2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and rs67376798 before treatment starts. We implemented the genotyping in our daily clinical r...
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| Published in | Pharmaceutics Vol. 16; no. 7; p. 956 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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MDPI AG
19.07.2024
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| Abstract | Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the
*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and
rs67376798 before treatment starts. We implemented the
genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the
rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of
testing for FP dose tailoring in our clinical practice and characterized the
gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the
test, and this dose tailoring does not affect the treatment efficacy. We also found that the
*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67;
= 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77;
= 0.019) among FP-treated patients based on the
genotype. This makes it a candidate variant for implementation in clinical practice. |
|---|---|
| AbstractList | Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35–23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41–28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice. Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice. Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the *2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and rs67376798 before treatment starts. We implemented the genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of testing for FP dose tailoring in our clinical practice and characterized the gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the test, and this dose tailoring does not affect the treatment efficacy. We also found that the *4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67; = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77; = 0.019) among FP-treated patients based on the genotype. This makes it a candidate variant for implementation in clinical practice. |
| Author | Ruiz-Tueros, Gabriela Morón, Rocío González Astorga, Beatriz Iáñez, Antonio J Cabeza-Barrera, José Díaz-Villamarín, Xando Fernández-Varón, Emilio Blancas, Isabel Nieto-Sánchez, María Teresa Torres-García, Alicia Martínez-Pérez, María |
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| References | Meinsma (ref_8) 1995; 14 Lam (ref_27) 2016; 50 Henricks (ref_3) 2017; 28 Meulendijks (ref_13) 2015; 16 Henricks (ref_2) 2018; 19 Huddart (ref_14) 2021; 110 Lacasana (ref_25) 2015; 139 ref_32 Blom (ref_9) 1997; 20 ref_17 ref_16 ref_15 Sharma (ref_12) 2021; 26 Lee (ref_31) 2014; 106 Miwa (ref_6) 1998; 34 Lunenburg (ref_19) 2020; 28 Twelves (ref_4) 2001; 19 Fragoulakis (ref_33) 2023; 197 Freeman (ref_24) 2003; 33 Eisenhauer (ref_22) 2009; 45 Deenen (ref_11) 2016; 34 Wei (ref_10) 1996; 98 White (ref_5) 2022; 112 Deenen (ref_26) 2011; 17 Madi (ref_29) 2018; 102 Amstutz (ref_18) 2018; 103 ref_21 ref_20 Valls (ref_23) 2006; 22 Koufaki (ref_34) 2023; 17 Seck (ref_28) 2005; 11 Mikhail (ref_1) 2010; 9 Meinsma (ref_7) 2003; 9 Kuilenburg (ref_30) 2016; 1862 |
| References_xml | – volume: 98 start-page: 610 year: 1996 ident: ref_10 article-title: Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity publication-title: J. Clin. Investig. doi: 10.1172/JCI118830 contributor: fullname: Wei – volume: 26 start-page: 1008 year: 2021 ident: ref_12 article-title: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis publication-title: Oncologist doi: 10.1002/onco.13967 contributor: fullname: Sharma – volume: 110 start-page: 563 year: 2021 ident: ref_14 article-title: An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine publication-title: Clin. Pharmacol. Ther. doi: 10.1002/cpt.2350 contributor: fullname: Huddart – volume: 34 start-page: 1274 year: 1998 ident: ref_6 article-title: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5 fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue publication-title: Eur. J. Cancer doi: 10.1016/S0959-8049(98)00058-6 contributor: fullname: Miwa – volume: 20 start-page: 331 year: 1997 ident: ref_9 article-title: The activity of dihydropyrimidine dehydrogenase in human blood cells publication-title: J. Inherit. Metab. Dis. doi: 10.1023/A:1005305323052 contributor: fullname: Blom – volume: 19 start-page: 1459 year: 2018 ident: ref_2 article-title: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: A prospective safety analysis publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(18)30686-7 contributor: fullname: Henricks – volume: 106 start-page: dju298 year: 2014 ident: ref_31 article-title: DPYD variants as predictors of 5-fluorouracil toxicity in adjuvant colon cancer treatment (NCCTG N0147) publication-title: J. Natl. Cancer Inst. doi: 10.1093/jnci/dju298 contributor: fullname: Lee – volume: 197 start-page: 106949 year: 2023 ident: ref_33 article-title: Cost-utility analysis and cross-country comparison of pharmacogenomics-guided treatment in colorectal cancer patients participating in the U-PGx PREPARE study publication-title: Pharmacol. Res. doi: 10.1016/j.phrs.2023.106949 contributor: fullname: Fragoulakis – ident: ref_16 – volume: 11 start-page: 5886 year: 2005 ident: ref_28 article-title: Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in a cohort of Caucasian individuals publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-04-1784 contributor: fullname: Seck – volume: 22 start-page: 1928 year: 2006 ident: ref_23 article-title: SNPStats: A web tool for the analysis of association studies publication-title: Bioinformatics doi: 10.1093/bioinformatics/btl268 contributor: fullname: Valls – ident: ref_21 – ident: ref_20 doi: 10.1371/journal.pone.0028096 – volume: 103 start-page: 210 year: 2018 ident: ref_18 article-title: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update publication-title: Clin. Pharmacol. Ther. doi: 10.1002/cpt.911 contributor: fullname: Amstutz – volume: 1862 start-page: 754 year: 2016 ident: ref_30 article-title: Phenotypic and clinical implications of variants in the dihydropyrimidine dehydrogenase gene publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbadis.2016.01.009 contributor: fullname: Kuilenburg – volume: 28 start-page: 2915 year: 2017 ident: ref_3 article-title: DPYD genotype-guided dose individualization to improve patient safety of fluoropyrimidine therapy: Call for a drug label update publication-title: Ann. Oncol. doi: 10.1093/annonc/mdx411 contributor: fullname: Henricks – volume: 17 start-page: 51 year: 2023 ident: ref_34 article-title: Economic evaluation of pharmacogenomic-guided antiplatelet treatment in Spanish patients suffering from acute coronary syndrome participating in the U-PGx PREPARE study publication-title: Hum. Genom. doi: 10.1186/s40246-023-00495-3 contributor: fullname: Koufaki – volume: 139 start-page: 534 year: 2015 ident: ref_25 article-title: Polymorphisms of pesticide-metabolizing genes in children living in intensive farming communities publication-title: Chemosphere doi: 10.1016/j.chemosphere.2015.07.079 contributor: fullname: Lacasana – volume: 14 start-page: 1 year: 1995 ident: ref_8 article-title: Human polymorphism in drug metabolism: Mutation in the dihydropyrimidine dehydrogenase gene results in exon skipping and thymine uracilurea publication-title: DNA Cell Biol. doi: 10.1089/dna.1995.14.1 contributor: fullname: Meinsma – volume: 50 start-page: 9 year: 2016 ident: ref_27 article-title: The role of pharmacogenetics in capecitabine efficacy and toxicity publication-title: Cancer Treat. Rev. doi: 10.1016/j.ctrv.2016.08.001 contributor: fullname: Lam – ident: ref_15 doi: 10.1038/nature11632 – volume: 33 start-page: 67 year: 2003 ident: ref_24 article-title: DNA from buccal swabs recruited by mail: Evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping publication-title: Behav. Genet. doi: 10.1023/A:1021055617738 contributor: fullname: Freeman – volume: 102 start-page: 31 year: 2018 ident: ref_29 article-title: Pharmacogenetic analyses of 2183 patients with advanced colorectal cancer; potential role for common dihydropyrimidine dehydrogenase variants in toxicity to chemotherapy publication-title: Eur. J. Cancer doi: 10.1016/j.ejca.2018.07.009 contributor: fullname: Madi – volume: 34 start-page: 227 year: 2016 ident: ref_11 article-title: Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2015.63.1325 contributor: fullname: Deenen – volume: 28 start-page: 508 year: 2020 ident: ref_19 article-title: Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines publication-title: Eur. J. Hum. Genet. doi: 10.1038/s41431-019-0540-0 contributor: fullname: Lunenburg – volume: 17 start-page: 3455 year: 2011 ident: ref_26 article-title: Relationship between single nucleotide polymorphisms and haplotypes in DPYD and toxicity and efficacy of capecitabine in advanced colorectal cancer publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-10-2209 contributor: fullname: Deenen – ident: ref_17 – volume: 19 start-page: 4097 year: 2001 ident: ref_4 article-title: Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: Results of a large phase III study publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2001.19.21.4097 contributor: fullname: Twelves – volume: 9 start-page: 831 year: 2010 ident: ref_1 article-title: Safety of capecitabine: A review publication-title: Expert. Opin. Drug Saf. doi: 10.1517/14740338.2010.511610 contributor: fullname: Mikhail – volume: 112 start-page: 791 year: 2022 ident: ref_5 article-title: Dihydropyrimidine Dehydrogenase Deficiency and Implementation of Upfront DPYD Genotyping publication-title: Clin. Pharmacol. Ther. doi: 10.1002/cpt.2667 contributor: fullname: White – volume: 45 start-page: 228 year: 2009 ident: ref_22 article-title: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) publication-title: Eur. J. Cancer doi: 10.1016/j.ejca.2008.10.026 contributor: fullname: Eisenhauer – volume: 9 start-page: 4363 year: 2003 ident: ref_7 article-title: Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity publication-title: Clin. Cancer Res. contributor: fullname: Meinsma – ident: ref_32 doi: 10.1016/j.biopha.2023.115706 – volume: 16 start-page: 1639 year: 2015 ident: ref_13 article-title: Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: A systematic review and meta-analysis of individual patient data publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(15)00286-7 contributor: fullname: Meulendijks |
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| Snippet | Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the
*2A (rs3918290),... Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A... |
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| SubjectTerms | clinical implementation Clinical medicine Cytotoxicity Dehydrogenases DPYD Drug dosages Enzymes fluoropyrimidines Genotype & phenotype Metabolites personalized medicine pharmacogenetics Toxicity |
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| Title | Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/39065653 https://www.proquest.com/docview/3085036761 https://www.proquest.com/docview/3085120800 https://doaj.org/article/375500f0990a4cdda0725be18846d843 |
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