期刊
CANCER BIOLOGY & THERAPY
卷 1, 期 6, 页码 669-673出版社
LANDES BIOSCIENCE
DOI: 10.4161/cbt.318
关键词
thalidomide; cytochrome P450; metabolism; pharmacogenetics; prostate cancer
类别
Thalidomide requires cytochrome P450 (CYP)catalyzed biotransformation for its antiangiogenic property, and CYP2C19 is responsible for 5-hydroxylation and 5'-hydroxylation of thalidomide in human. This study explored a hypothesis that patients with poor metabolizing phenotype of CYP2C19 receive little benefit from thalidomide treatment and that the poor metabolizer genotype is associated with lower ability to form the metabolites. A case-control study was conducted with 63 patients with prostate cancer who had been enrolled in a randomized phase II trial of thalidomide monotherapy (200 to 1,200 mg/day). CYP2C19 polymorphism (CYP2C19*2, CYP2C19*3, CYP2C19*4) was compared with clinical events (prostate-specific antigen (PSA) decline) and formations of the hydroxylated metabolites. Two patients were homozygous for the variant CYP2C19*2 allele (poor metabolizing phenotype). Both of these were included in the 25 patients whose PSA failed to demonstrate a decline. While 32% and 48% of the patients had quantifiable levels of 5-hydroxythalidomide and cis-5'-hydroxythalidomide, respectively, these metabolite were below quantification in both poor metabolizing patients. None had CYP2C19*3 or CYP2C19*4 alleles. Although this study had no power to detect the statistical significance of the CYP2C19 genotype, the findings were consistent with our hypothesis. The role of CYP2C19 polymorphism in thalidomide treatments remains to be elucidated.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据