Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper.
Antimetabolites, Antineoplastic
/ administration & dosage
Austria
Capecitabine
/ administration & dosage
Consensus
Dihydrouracil Dehydrogenase (NADP)
/ genetics
Female
Fluorouracil
/ administration & dosage
Genetic Testing
/ methods
Genotype
Germany
Humans
Male
Mutation
Neoplasms
/ drug therapy
Phenotype
Practice Guidelines as Topic
Switzerland
Tegafur
/ administration & dosage
5-Fluorouacil
Capecitabine
Dihydropyrimidine dehydrogenase mutation
Genetic testing
Tegafur
Journal
Oncology research and treatment
ISSN: 2296-5262
Titre abrégé: Oncol Res Treat
Pays: Switzerland
ID NLM: 101627692
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
07
2020
accepted:
17
07
2020
pubmed:
26
10
2020
medline:
3
3
2021
entrez:
25
10
2020
Statut:
ppublish
Résumé
5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%. Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.
Sections du résumé
BACKGROUND
BACKGROUND
5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%.
SUMMARY
CONCLUSIONS
Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.
Identifiants
pubmed: 33099551
pii: 000510258
doi: 10.1159/000510258
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Tegafur
1548R74NSZ
Capecitabine
6804DJ8Z9U
Dihydrouracil Dehydrogenase (NADP)
EC 1.3.1.2
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
628-636Informations de copyright
© 2020 S. Karger AG, Basel.