title: Genetic variation of CYP3A5 influences paclitaxel/carboplatin-induced toxicity in Chinese epithelial ovarian cancer patients.
abstract: Combination chemotherapy with platinum and taxane is the first-line treatment for ovarian cancer. The dose-limiting toxicities of these drugs include neuropathy, leukopenia, and neutropenia, but they exhibit substantial interindividual variability. This study investigated the relationship between CYP3A5 polymorphisms and paclitaxel/carboplatin-induced toxicity in Chinese epithelial ovarian cancer patients. Seventy-five patients with epithelial ovarian cancer were recruited. After combination chemotherapy, genotype analysis was conducted, and toxic effects were evaluated according to the Common Toxicity Criteria. A significant association was found between myelosuppression and the CYP3A5*3 genotype. CYP3A5*3/*1 patients showed a significantly higher risk of developing leukopenia (P < .001; Pearson's χ(2) test) and neutropenia (P < .001; Pearson's χ(2) test) than CYP3A5*3*3 patients. CYP3A5*3/*3 patients had significantly higher median leukocyte and neutrophil nadir counts than CYP3A5*3*1 patients (P < .001, Mann-Whitney U test). However, we did not observe an association between neuropathy and CYP3A5*3 in this study (P =.64; Pearson's χ(2) test). This is the first study to verify the influence of CYP3A5 polymorphisms on paclitaxel/carboplatin-induced toxicity in Chinese epithelial ovarian cancer patients. Our findings suggest that interindividual variability in paclitaxel/carboplatin-induced myelosuppression can be predicted by CYP3A5*3 genotyping and that incorporation of CYP3A5*3 genetic data in treatment selection could help to reduce myelosuppression events, thereby individualizing paclitaxel/carboplatin pharmacotherapy.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, People's Republic of China.
authors.forename: Qiao-Li
authors.initials: QL
authors.lastname: Lv
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, People's Republic of China.
authors.forename: Na-Yiyuan
authors.initials: NY
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Chong-Zhen
authors.initials: CZ
authors.lastname: Qin
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, People's Republic of China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000009:adverse effects*; D000077216:Carcinoma, Ovarian Epithelial; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics*; D009504:Neutrophils / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017239:Paclitaxel / Q000009:adverse effects*; D010292:Paresthesia / Q000139:chemically induced; D000071184:Pharmacogenomic Variants / Q000187:drug effects / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D016190:Carboplatin; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D017239:Paclitaxel
keywords: CYP3A5; Paclitaxel; myelosuppression; ovarian cancer; toxicity