克里唑替尼治疗晚期非小细胞肺癌的临床研究进展

Clinical Research of Crizotinib in Advanced Non-small Cell Lung Cancer

目前在非小细胞肺癌(non-small cell lung cancer,NSCLC)的治疗中,靶向药物治疗占有举足轻重的地位。继表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI)之后,针对棘皮动物微管相关蛋白4-间变性淋巴瘤激酶(echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase,EML4-ALK)融合基因突变为靶点的克里唑替尼(crizotinib)成为了NSCLC靶向治疗领域的焦点。Ⅰ期、Ⅱ期临床试验均已证实:crizotinib治疗EML4-ALK阳性晚期NSCLC患者有效,并能改善患者症状,毒副作用小,患者耐受性较好。近期发现crizotinib对ROS1受体酪氨酸激酶也具有抑制作用。Crizotinib在ROS1基因重排NSCLC中显示出了非常明显的抗肿瘤活性。与其它TKIs一样,crizotinib也存在耐药现象,其耐药机制待进一步研究。现就crizotinib作用机制、药代动力学及治疗晚期NSCLC的临床研究进展做一综述。

At present, in the treatment of non-small cell lung cancer （NSCLC）, targeted therapy has an important status. After epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKIs）, crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC. Phase I and II clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients, little side-effect, and well tolerated. Recently, crizotinib can inhibit ROS1 receptor tyrosine kinase and show extraordinary significant antitumor activity in ROS1-rearranged NSCLC. Drug resistance also exists in crizotinib. The mechanism of drug resistance needs further research. In this study, a review is performed in the mechanism and pharmacokinetics of crizotinib, and the clinical progress of treatment in advanced NSCLC.