Zhu Haibo, Xu Xiaoyu, Wang Ling
Dalian Medical University, Dalian 116044, China.
Zhongguo Fei Ai Za Zhi. 2013 Jun;16(6):321-4. doi: 10.3779/j.issn.1009-3419.2013.06.09.
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.
目前,在非小细胞肺癌(NSCLC)的治疗中,靶向治疗具有重要地位。继表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)之后,针对EML4-ALK融合基因的克唑替尼成为NSCLC分子靶向治疗的一种重要药物。Ⅰ期和Ⅱ期临床试验证明,克唑替尼对晚期NSCLC患者中激活的EML4-ALK突变的治疗有效,副作用小,耐受性良好。最近,克唑替尼可抑制ROS1受体酪氨酸激酶,并在ROS1重排的NSCLC中显示出非常显著的抗肿瘤活性。克唑替尼也存在耐药性。耐药机制有待进一步研究。本研究对克唑替尼的作用机制、药代动力学以及晚期NSCLC治疗的临床进展进行综述。