Format

Send to

Choose Destination
Bull Cancer. 2018 Apr;105(4):397-407. doi: 10.1016/j.bulcan.2018.02.001. Epub 2018 Feb 24.

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

[Article in French]

Author information

1
AP-HP, hôpital européen Georges-Pompidou, service de biochimie, 20, rue Leblanc, 75015 Paris, France.
2
AP-HM, hôpital La Timone, laboratoire de pharmacocinétique et toxicologie, 264, rue Saint-Pierre, 13005 Marseille, France.
3
Laboratoire de pharmacologie, CLCC Claudius-Regaud, IUCT-Oncopole, 1, avenue Irène-Joliot-Curie, 31100 Toulouse, France.
4
CHU Bretonneau, Laboratoire de biochimie et biologie moléculaire, 2, boulevard Tonnellé, 37000 Tours, France.
5
CHU Jean-Minjoz, laboratoire de pharmacologie clinique et toxicologie, 3, boulevard Alexandre-Fleming, 25030 Besançon, France.
6
Laboratoire d'oncopharmacologie, centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice cedex 2, France.
7
CHU de Limoges, service de pharmacologie, toxicologie et pharmacovigilance, 2, avenue Martin-Luther-King, 87000 Limoges, France.
8
Assistance publique-Hôpitaux de Paris, service de génétique moléculaire, pharmacogénétique et hormonologie, Inserm UMR S1178, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France.
9
Service pharmacie, centre Georges-François-Leclerc, 1, rue du Professeur-Mario, 21000 Dijon, France.
10
Département de biopathologie, ICO, René-Gauducheau, 44805 Nantes-Saint-Herblain, France.
11
Université de Lorraine, institut de cancérologie de Lorraine, CNRS UMR7039 CRAN, 6, avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.
12
Gustave-Roussy Cancer campus, service de pharmacologie, 114, rue Edouard-Vaillant, 94800 Villejuif, France.
13
CHU Carémeau, laboratoire de biochimie et biologie moléculaire, rue du Professeur-Debré, 30900 Nîmes, France.
14
CHU de Lille, service de toxicologie-génopathies, 2, avenue Oscar-Lambret, 59000 Lille, France.
15
CHU Grenoble-Alpes, institut de biologie et pathologie, laboratoire de pharmacologie, pharmacogénétique et toxicologie, avenue Maquis-du-Grésivaudan, 38700 La Tronche, France.
16
CHU La Milétrie, laboratoire de génétique, service de pharmacologie clinique et vigilances, 2, rue de la Milétrie, 86021 Poitiers, France.
17
Centre hospitalier Lyon-Sud, HCL, service de biochimie et biologie moléculaire, 165, chemin du Grand-Revoyet, 69310 Pierre-Bénite, France.
18
Centre randomisation gestion-analyse, fédération francophone de cancérologie digestive, 7, boulevard Jeanne-d'Arc, 21000 Dijon, France.
19
Laboratoire d'oncopharmacologie, centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice cedex 2, France. Electronic address: marie-christine.etienne@nice.unicancer.fr.

Abstract

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.

KEYWORDS:

5-Fluorouracile; 5Fluorouracil; Capecitabine; Capécitabine; DPYD; Dihydropyrimidine dehydrogenase; Dihydropyrimidine déshydrogénase; Dépistage; Fluoropyrimidine; Pharmacogenetics; Pharmacogénétique; Recommandation; Recommendation; Screening; Toxicity; Toxicité

PMID:
29486921
DOI:
10.1016/j.bulcan.2018.02.001
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center