Titre :

Dihydropyrimidine déhydrogenase (DPD) deficiency screening and securing of fluoropyrimidine-based chemotherapies: Update and recommendations of the French GPCO-Unicancer and RNPGx networks

Auteur(s) :

Loriot, Marie-Anne [Auteur]
Ciccolini, Joseph [Auteur]
Thomas, Fabienne [Auteur]
Barin-Le-Guellec, Chantal [Auteur]
Royer, Bernard [Auteur]
Milano, Gerard [Auteur]
Picard, Nicolas [Auteur]
Becquemont, Laurent [Auteur]
Verstuyft, Celine [Auteur]
Narjoz, Celine [Auteur]
Schmitt, Antonin [Auteur]
Bobin-Dubigeon, Christine [Auteur]
Harle, Alexandre [Auteur]
Paci, Angelo [Auteur]
Poinsignon, Vianney [Auteur]
Quaranta, Sylvie [Auteur]
Evrard, Alexandre [Auteur]
Hennart, Benjamin [Auteur]
Broly, Franck [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Fonrose, Xavier [Auteur]
Lafay-Chebassier, Claire [Auteur]
Wozny, Anne-Sophie [Auteur]
Masskouri, Fadil [Auteur]
Boyer, Jean-Christophe [Auteur]
Etienne-Grimaldi, Marie-Christine [Auteur]

Titre de la revue :

Bulletin du cancer

Nom court de la revue :

Bull Cancer

Date de publication :

2018-02-24

ISSN :

1769-6917

Mot(s)-clé(s) :

5Fluorouracil
Fluoropyrimidine
Capecitabine
Dihydropyrimidine dehydrogenase
DPYD
Screening
Toxicity
Recommendation
Pharmacogenetics

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Fluoropyrimidines (FU) are still the most prescribed anticancer drugs for the treatment of solid cancers. However, fluoropyrimidines cause severe toxicities in 10 to 40% of patients and toxic deaths in 0.2 to 0.8% of ...
Lire la suite >Fluoropyrimidines (FU) are still the most prescribed anticancer drugs for the treatment of solid cancers. However, fluoropyrimidines cause severe toxicities in 10 to 40% of patients and toxic deaths in 0.2 to 0.8% of patients, resulting in a real public health problem. The main origin of FU-related toxicities is a deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme of 5-FU catabolism. DPD deficiency may be identified through pharmacogenetics testing including phenotyping (direct or indirect measurement of enzyme activity) or genotyping (detection of inactivating polymorphisms on the DPYD gene). Approximately 3 to 15% of patients exhibit a partial deficiency and 0.1 to 0.5% a complete DPD deficiency. Currently, there is no regulatory obligation for DPD deficiency screening in patients scheduled to receive a fluoropyrimidine-based chemotherapy. Based on the levels of evidence from the literature data and considering current French practices, the Group of Clinical Pharmacology in Oncology (GPCO)-UNICANCER and the French Network of Pharmacogenetics (RNPGx) recommend the following: (1) to screen DPD deficiency before initiating any chemotherapy containing 5-FU or capecitabine; (2) to perform DPD phenotyping by measuring plasma uracil (U) concentrations (possibly associated with dihydrouracil/U ratio), and DPYD genotyping (variants *2A, *13, p.D949V, HapB3); (3) to reduce the initial FU dose (first cycle) according to DPD status, if needed, and further, to consider increasing the dose at subsequent cycles according to treatment tolerance. In France, 17 public laboratories currently undertake routine screening of DPD deficiency.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Institut Pasteur de Lille
Université de Lille

Collections :

• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483

Date de dépôt :

2022-02-02T10:23:32Z