Department Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland.
Clin Lung Cancer. 2013 Sep;14(5):473-80. doi: 10.1016/j.cllc.2013.04.006. Epub 2013 Jun 20.
An anaplastic lymphoma kinase (ALK) translocation giving rise to activated ALK tyrosine kinase is present in approximately 5% of non-small-cell lung cancers (NSCLCs). Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, met proto-oncogene, and c-ros oncogene 1 (ROS1). It was recently approved in several countries for the treatment of patients with advanced, ALK-rearranged NSCLC. In 2012, results from the first phase III trial showing superiority of crizotinib compared with standard chemotherapy in second-line treatment of ALK-positive NSCLC were presented. Furthermore, crizotinib was recently shown to be active in ROS1-rearranged NSCLC. Here, we give an overview of the molecular pathogenesis of ALK-rearranged NSCLC, the pharmacokinetic and pharmacodynamic properties of crizotinib, and clinical trials of crizotinib for ALK-rearranged NSCLC.
间变性淋巴瘤激酶 (ALK) 易位导致激活的 ALK 酪氨酸激酶的存在大约占非小细胞肺癌 (NSCLC) 的 5%。克唑替尼是一种针对 ALK、间质表皮转化因子 (MET) 原癌基因和 c-ros 原癌基因 1 (ROS1) 的口服酪氨酸激酶抑制剂。它最近在多个国家被批准用于治疗晚期、ALK 重排的 NSCLC 患者。2012 年，首次 III 期试验结果表明，与标准化疗相比，克唑替尼在二线治疗 ALK 阳性 NSCLC 方面具有优越性。此外，克唑替尼最近在 ROS1 重排的 NSCLC 中显示出活性。在这里，我们概述了 ALK 重排 NSCLC 的分子发病机制、克唑替尼的药代动力学和药效学特性，以及克唑替尼治疗 ALK 重排 NSCLC 的临床试验。
