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

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

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

アブストラクト	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.
ジャーナル名	Bulletin du cancer
Pubmed追加日	2018/3/1
投稿者	Loriot, Marie-Anne; Ciccolini, Joseph; Thomas, Fabienne; Barin-Le-Guellec, Chantal; Royer, Bernard; Milano, Gerard; Picard, Nicolas; Becquemont, Laurent; Verstuyft, Celine; Narjoz, Celine; Schmitt, Antonin; Bobin-Dubigeon, Christine; Harle, Alexandre; Paci, Angelo; Poinsignon, Vianney; Quaranta, Sylvie; Evrard, Alexandre; Hennart, Benjamin; Broly, Franck; Fonrose, Xavier; Lafay-Chebassier, Claire; Wozny, Anne-Sophie; Masskouri, Fadil; Boyer, Jean-Christophe; Etienne-Grimaldi, Marie-Christine
組織名	AP-HP, hopital europeen Georges-Pompidou, service de biochimie, 20, rue Leblanc,;75015 Paris, France.;AP-HM, hopital La Timone, laboratoire de pharmacocinetique et toxicologie, 264,;rue Saint-Pierre, 13005 Marseille, France.;Laboratoire de pharmacologie, CLCC Claudius-Regaud, IUCT-Oncopole, 1, avenue;Irene-Joliot-Curie, 31100 Toulouse, France.;CHU Bretonneau, Laboratoire de biochimie et biologie moleculaire, 2, boulevard;Tonnelle, 37000 Tours, France.;CHU Jean-Minjoz, laboratoire de pharmacologie clinique et toxicologie, 3,;boulevard Alexandre-Fleming, 25030 Besancon, France.;Laboratoire d'oncopharmacologie, centre Antoine-Lacassagne, 33, avenue de;Valombrose, 06189 Nice cedex 2, France.;CHU de Limoges, service de pharmacologie, toxicologie et pharmacovigilance, 2,;avenue Martin-Luther-King, 87000 Limoges, France.;Assistance publique-Hopitaux de Paris, service de genetique moleculaire,;pharmacogenetique et hormonologie, Inserm UMR S1178, 78, rue du General-Leclerc,;94270 Le Kremlin-Bicetre, France.;Service pharmacie, centre Georges-Francois-Leclerc, 1, rue du Professeur-Mario,;21000 Dijon, France.;Departement de biopathologie, ICO, Rene-Gauducheau, 44805 Nantes-Saint-Herblain,;France.;Universite de Lorraine, institut de cancerologie de Lorraine, CNRS UMR7039 CRAN,;6, avenue de Bourgogne, 54519 Vandoeuvre-les-Nancy, France.;Gustave-Roussy Cancer campus, service de pharmacologie, 114, rue;Edouard-Vaillant, 94800 Villejuif, France.;CHU Caremeau, laboratoire de biochimie et biologie moleculaire, rue du;Professeur-Debre, 30900 Nimes, France.;CHU de Lille, service de toxicologie-genopathies, 2, avenue Oscar-Lambret, 59000;Lille, France.;CHU Grenoble-Alpes, institut de biologie et pathologie, laboratoire de;pharmacologie, pharmacogenetique et toxicologie, avenue Maquis-du-Gresivaudan,;38700 La Tronche, France.;CHU La Miletrie, laboratoire de genetique, service de pharmacologie clinique et;vigilances, 2, rue de la Miletrie, 86021 Poitiers, France.;Centre hospitalier Lyon-Sud, HCL, service de biochimie et biologie moleculaire,;165, chemin du Grand-Revoyet, 69310 Pierre-Benite, France.;Centre randomisation gestion-analyse, federation francophone de cancerologie;digestive, 7, boulevard Jeanne-d'Arc, 21000 Dijon, France.;Valombrose, 06189 Nice cedex 2, France. Electronic address:;marie-christine.etienne@nice.unicancer.fr.
Pubmed リンク	https://www.ncbi.nlm.nih.gov/pubmed/29486921/