Determinants of Gefitinib toxicity in advanced non-small cell lung cancer (NSCLC): a pharmacogenomic study of metabolic enzymes and transporters
Determinants of Gefitinib toxicity in advanced non-small cell lung cancer (NSCLC): a pharmacogenomic study of metabolic enzymes and transporters
复制标题
晚期非小细胞肺癌 (NSCLC) 中吉非替尼毒性的决定因素：代谢酶和转运蛋白的药物基因组学研究
DOI：
10.1038/tpj.2016.31
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发表时间：
2017-07-01
影响因子：
2.8
通讯作者：
Wang, X.
中科院分区：
文献类型：
--
作者：
Ma, Y.;Xin, S.;Wang, X.
Skin rash, diarrhea and hepatotoxicity are the most common toxicities of Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The present study investigated the effects of genetic polymorphisms of drug target, metabolizing enzymes and transporters on Gefitinib toxicities. Thirty single-nucleotide polymorphisms, including EGFR, cytochromes P450 and ATP-binding cassette (ABC), were genotyped by matrix-assisted laser desorption/ionization time-of-flight platform in 59 non-small cell lung cancer patients treated with Gefitinib. Correlation analyses were performed to evaluate their effects on Gefitinib-induced toxicities. ABCB1 rs1128503 TT genotype was a significant high-risk determinant of both skin rash and diarrhea, with 15.78-and 10.78-fold of incident risk increased, respectively.(odds ratio (OR)= 15.78, 95% confidence interval (CI) 2.01–124.1, P= 0.0087; OR= 10.78, 95% CI 1.54–75.40, P= 0.0166 vs non-TT genotypes). Patients with ABCB1 rs1128503 TT genotype had greater risk of skin rash and diarrhea. Therefore, polymorphism analyses of ABCB1 might be beneficial to optimize Gefitinib treatment.
