[Detection of dihydropyrimidine dehydrogenase deficiency before treatment by fluoropyrimidines].
Numerous toxic side-effects, sometimes severe, are regularly reported in patients treated with 5-fluorouracil, and oral fluoropyrimidines, UFT and capecitabine, in metastatic and adjuvant setting. These toxic effects are due to a large interindividual variability of the metabolism, mainly depending on dihydropyrimidine dehydrogenase activity (DPD), the major enzyme of the catabolism of fluoropyrimidines. Thus, the patients with a DPD deficiency are at high risk of early severe acute toxicity, with this kind of drug. These toxic side-effects are potentially lethal. DPD deficiency frequencies, partial or complete, are about 3-5% and 0.2% respectively. They are most often due to a gene polymorphism. Different techniques for the detection of DPD deficiency before treatment have been reported: phenotypic, such as the plasma ratio of dihydrouracil/uracil, or genotypic, such as the detection of DPD gene variants, deleterious for enzyme activity. The pretherapeutic detection of DPD deficiency would permit to avoid almost every early acute toxic side-effects. We must emphasize that it is not merely a genetic result, since the detection of a deficiency most often does not contra-indicate the use of a fluoropyrimidine, but it must be combined with therapeutic advice.
Gamelin
Erick
E
Département d'Oncopharmacologie-Pharmacogénétique, INSERM U564, Centre Régional de Lutte Contre le Cancer Paul Papin, 2 rue Moll, 49033 Angers Cedex 9, France. e.gamelin@unimedia.fr
Boisdron-Celle
Michèle
M
Morel
Alain
A
D000970:Antineoplastic Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005641:Tegafur / Q000009:adverse effects; D014498:Uracil / Q000009:adverse effects
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005641:Tegafur; D014498:Uracil; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil