Au Trang H, Cavalieri Courtney C, Stenehjem David D
1 Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
2 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
J Oncol Pharm Pract. 2017 Dec;23(8):602-614. doi: 10.1177/1078155216672315. Epub 2016 Oct 13.
Clinical pharmacists are important contributors to the care of patients with cancer; it is therefore critical for oncology clinical pharmacists to stay current with new anticancer therapies. This review summarizes the epidemiology and pathogenesis of non-small cell lung cancer, including the most common genetic alterations, as well as the mechanism of action, clinical development, pharmacodynamics and pharmacokinetics of the anaplastic lymphoma kinase inhibitor ceritinib for the treatment of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer. Targeted therapies based on the presence of specific mutations are an important development in the treatment of non-small cell lung cancer. However, acquired resistance to the first anaplastic lymphoma kinase-inhibitor approved by the U.S. Food and Drug Administration, crizotinib, is observed in almost half of patients treated with it. Ceritinib is an oral anaplastic lymphoma kinase-inhibitor that has demonstrated more potent antitumor activity than crizotinib in preclinical models. It was granted accelerated approval in 2014 to treat anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer patients who have progressed on or are intolerant to crizotinib. Ceritinib represents an important alternative second-line therapy for patients with metastatic non-small cell lung cancer who have traditionally limited treatment options.
临床药师是癌症患者护理的重要贡献者；因此，肿瘤临床药师紧跟新的抗癌疗法至关重要。本综述总结了非小细胞肺癌的流行病学和发病机制，包括最常见的基因改变，以及间变性淋巴瘤激酶抑制剂色瑞替尼用于治疗间变性淋巴瘤激酶阳性非小细胞肺癌患者的作用机制、临床开发、药效学和药代动力学。基于特定突变的靶向治疗是非小细胞肺癌治疗的一项重要进展。然而，在美国食品药品监督管理局批准的首个间变性淋巴瘤激酶抑制剂克唑替尼治疗的患者中，几乎有一半观察到获得性耐药。色瑞替尼是一种口服间变性淋巴瘤激酶抑制剂，在临床前模型中已显示出比克唑替尼更强的抗肿瘤活性。2014年，它被加速批准用于治疗对克唑替尼进展或不耐受的间变性淋巴瘤激酶阳性转移性非小细胞肺癌患者。对于传统上治疗选择有限的转移性非小细胞肺癌患者，色瑞替尼是一种重要的二线替代疗法。
