Pearson Rachel, Kolesar Jill M
Division of Pharmacy Practice, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
J Oncol Pharm Pract. 2012 Jun;18(2):271-4. doi: 10.1177/1078155211417477. Epub 2011 Aug 15.
The purpose of this review article is to describe the emerging data of ALK receptor tyrosine kinaase inhibitors in ALK mutation positive NSCLC.
ALK mutations have been identified in approximately 2.4-13% of patients with NSCLC, occurring more frequently in adenocarcinomas and never and light smokers. Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations. A phase II study demonstrated an overall response rate of 57% (95% CI, 46 to 68), with the most common toxicity grade I fatigue and visual disturbances. Elevations in lever function tests were also reported.
The ALK receptor tyrosine kinase inhibitor crizotinib may be an effective therapy in ALK mutated NSCLC and is currently being compared to standard chemotherapy for advanced or metastatic NSCLC.
这篇综述文章的目的是描述ALK受体酪氨酸激酶抑制剂在ALK突变阳性非小细胞肺癌中的新出现的数据。
在大约2.4%-13%的非小细胞肺癌患者中已鉴定出ALK突变，在腺癌以及从不吸烟和轻度吸烟患者中更频繁发生。克唑替尼是一种口服的ATP竞争性ALK和MET酪氨酸激酶选择性抑制剂，在纳摩尔浓度下可抑制活化的ALK的酪氨酸磷酸化。一项II期研究显示总缓解率为57%（95%CI，46至68），最常见的毒性为I级疲劳和视觉障碍。也报告了肝功能检查结果升高。
ALK受体酪氨酸激酶抑制剂克唑替尼可能是ALK突变的非小细胞肺癌的一种有效治疗方法，目前正在与晚期或转移性非小细胞肺癌的标准化疗进行比较。
