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Genetic variation of CYP3A5 influences paclitaxel/carboplatin‐induced toxicity in Chinese epithelial ovarian cancer patients
Author(s) -
Hu Lei,
Lv QiaoLi,
Guo Ying,
Cheng Lin,
Wu NaYiyuan,
Qin ChongZhen,
Zhou HongHao
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.587
Subject(s) - carboplatin , medicine , paclitaxel , leukopenia , ovarian cancer , oncology , neutropenia , taxane , toxicity , chemotherapy , gastroenterology , pharmacology , cancer , cisplatin , breast cancer
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.