Premium
Pharmacogenetics of CYP3A5 and effects of corticosteroids in children treated for acute lymphoblastic leukemia
Author(s) -
Dupont C.,
Medard Y.,
Cave H.,
Vilmer E.,
JacqzAigrain E.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.075
Subject(s) - pharmacogenetics , medicine , lymphoblastic leukemia , cyp3a5 , oncology , acute lymphocytic leukemia , pharmacology , leukemia , genotype , biology , genetics , gene
The treatment of children with acute lymphoblastic leukaemias (ALL) according to EORTC 58951 protocol is divided into 3 phases (induction, consolidation, maintenance). During the induction phase, patients are randomly assigned to receive either prednisone or dexamethasone (associated with anticancer drugs). The response to corticotherapy is evaluated by the quantification of the residual disease (RD) at day 35 of treatment and has an major impact on prognosis and treatment: patients with an RD lower than <10 −2 /100 000 cells are classified as responders). Corticosteroids are both substrats and inducers of cytochromes P4503A (CYP3A): among the three isoforms, CYP3A5 is under genetic control with 70% of Caucasians not expressing CYP3A5 and carrying 3 of the 7 mutations described (*2, *3, *6). In the present work, the impact of CYP3A5 genetic polymorphism on the initial response to corticosteroids was studied. 225 children with ALL received dexamethasone or prednisolone and were genotyped for CYP3A5 using a PCR‐RFLP method. Among them, 27 had RD>10 −2 /100 000 cells. The distribution of CYP3A genotypes was : *1/*1: 2,7%, *1/*3: 18,8% and *3/*3: 78,5%, in aggrement with already published data. CYP3A5*2 and *6 mutations were not found There was no difference in the response to corticosteroid treatment according to individual CYP3A5 genotypes or to the type of corticosteroid. Our results did not evidence an impact of CYP3A5 on the initial response to corticosteroids. Clinical Pharmacology & Therapeutics (2004) 75 , P20–P20; doi: 10.1016/j.clpt.2003.11.075