Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines.
Antimetabolites, Antineoplastic
/ administration & dosage
Capecitabine
/ administration & dosage
Dihydrouracil Dehydrogenase (NADP)
/ genetics
Drug Therapy
/ methods
Drug-Related Side Effects and Adverse Reactions
/ genetics
Fluorouracil
/ administration & dosage
Genetic Testing
/ methods
Humans
Pharmacogenomic Variants
Practice Guidelines as Topic
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
02
08
2018
accepted:
13
10
2019
revised:
07
10
2019
pubmed:
21
11
2019
medline:
1
5
2021
entrez:
21
11
2019
Statut:
ppublish
Résumé
Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual's starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered "essential", therefore directing DPYD testing prior to initiating fluoropyrimidines.
Identifiants
pubmed: 31745289
doi: 10.1038/s41431-019-0540-0
pii: 10.1038/s41431-019-0540-0
pmc: PMC7080718
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Capecitabine
6804DJ8Z9U
Dihydrouracil Dehydrogenase (NADP)
EC 1.3.1.2
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
508-517Références
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