EGFR―TKI致肝损伤研究进展.docVIP

EGFR―TKI致肝损伤研究进展 　　【摘要】 随着口服小分子EGFR抑制剂的发展，非小细胞肺癌（NSCLC）治疗有了新的选择。伴有EGFR活化突变的NSCLC患者对EGFR酪氨酸激酶抑制剂（EGFR-TKIs）敏感且有临床获益。第一代EGFR-TKIs是可逆的ATP竞争性抑制剂，如吉非替尼和厄洛替尼在NSCLC治疗的一线，二线和维持治疗中都显示了较好的疗效。肿瘤治疗中TKIs的应用大大避免了传统化疗药物的毒性，但也带来了新毒性的发生。由于EGFR-TKI主要通过肝脏代谢，因而严重的肝毒性逐渐被人们所重视。通过检索吉非替尼和厄洛替尼治疗NSCLC的重要临床研究，笔者发现EGFR-TKIs可导致高级别（3级或以上）的肝损伤发生，吉非替尼的发生率为1%～27.6%，而厄洛替尼发生率为不到8%。虽然厄洛替尼导致的高级别肝损伤发生率较低但并发症却很严重，同样需要十分重视。TKI的肝毒性作用机制目前仍不是很清楚，还需要更进一步的研究。因此笔者在临床实践中需要更加关注TKI可能导致的肝损伤。 　　【关键词】 EGFR-TKI； 肝损伤； 研究进展 　　Research Progress of Liver Injury Induced by EGFR-TKI/TIAN Hong.//Medical Innovation of China，2015，12（04）：152-156 　　【Abstract】 The development of orally active small molecule inhibitors of the epidermal growth factor receptor（EGFR） had led to new treatment options for non-small cell lung cancer （NSCLC）.Patients with activating mutations of the EGFR gene show sensitivity and clinical benefit from treatment with EGFR tyrosine kinase inhibitors （EGFR-TKls）.First generation reversible ATP-competitive EGFR-TKls， such as gefitinib and erlotinib， are effective as first， second-line or maintenance therapy.The use of TKIs have largely avoided the conventional toxicities of chemotherapeutic agents in the treatment of cancers.But other types of toxicities began to emerge.Such as Severe Hepatotoxicity was gradually noticed by people because EGFR-TKI is mainly metabolized in liver.Through searching some important studys of gefitinib and erlotinib， we found frequencies of high-grade （grade 3 or above） hepatic adverse events of EGFR-TKIs varies from 1% to 27.6%， as seen with gefitinib and less than 8% as seen with erlotinib in treat with NSCLC.Although hepatic toxicity of erlotinib is a rare but severe complication.Mechanism of TKI hepatotoxicity is still not very clear and further study need to be continued.We should pay more attention to the occurrence of hepatic injury in the clinical application of TKI. 　　【Key words】 EGFR-TKI； Liver injury； Research progress 　　First-author’s address：Shenyang the Forth