药学学报, 2019, 54(4): 601-610
引用本文:
林安琪, 陈雨晴, 陈心蕊, 游丹铭, 罗鹏, 张健. 第三代ALK抑制剂lorlatinib在非小细胞肺癌中的研究进展[J]. 药学学报, 2019, 54(4): 601-610.
LIN An-qi, CHEN Yu-qing, CHEN Xin-rui, YOU Dan-ming, LUO Peng, ZHANG Jian. Lorlatinib: a third generation ALK inhibitor for treatment of non-small cell lung carcinoma[J]. Acta Pharmaceutica Sinica, 2019, 54(4): 601-610.

第三代ALK抑制剂lorlatinib在非小细胞肺癌中的研究进展
林安琪, 陈雨晴, 陈心蕊, 游丹铭, 罗鹏, 张健
南方医科大学珠江医院肿瘤中心, 广东 广州 510280
摘要:
Lorlatinib(PF-06463922)是一种具有高度选择性且强效的第三代ALK(anaplastic lymphoma kinase,ALK)/ROS1(c-ros oncogene 1,receptor tyrosine kinase)双重抑制剂。2018年11月,美国食品药物监督管理局批准了lorlatinib用于治疗接受crizotinib和至少一种其他ALK抑制剂治疗之后疾病恶化,或接受alectinib或ceritinib作为第一个ALK抑制剂治疗但疾病恶化的晚期ALK阳性NSCLC患者。Ⅰ/Ⅱ期临床研究结果显示,其具有优异的抗肿瘤活性、强大的颅内治疗活性、良好的耐受性和安全性。本文分别从lorlatinib的化学结构、作用机制、药效动力学、药代动力学、用法和用量、临床研究、安全性以及未来的发展方向作系统性的综述,以期为临床实践提供参考价值和借鉴意义。
关键词:    劳拉替尼      ALK抑制剂      非小细胞肺癌      临床研究     
Lorlatinib: a third generation ALK inhibitor for treatment of non-small cell lung carcinoma
LIN An-qi, CHEN Yu-qing, CHEN Xin-rui, YOU Dan-ming, LUO Peng, ZHANG Jian
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
Abstract:
Lorlatinib (PF-06463922) is a highly selective and potent third generation anaplastic lymphoma kinase (ALK) inhibitor with dual activity against c-ros oncogene 1, a receptor tyrosine kinase (ROS1). In November 2018, the US Food and Drug Administration approved lorlatinib for treatment of disease progression in ALK-positive and late-stage NSCLC patients who receive the treatment with crizotinib and at least one of other ALK inhibitors; and those with disease progression after treatment of alectinib or ceritinib as the first ALK inhibitor. The results of phase I/Ⅱ clinical trials showed that it has effective initial anti-tumor activity, strong intracranial therapeutic activity, with less tolerance and safety issues. This paper systematically reviewed the chemical structure, mechanism of action, pharmacodynamics, pharmacokinetics, usage and dosage, clinical research, safety and upcoming research fields of lolatinib, to provide an update on clinical or laboratory research and clinical practice.
Key words:    lorlatinib    anaplastic lymphoma kinase inhibitor    non-small cell lung cancer    clinical trial   
收稿日期: 2018-11-11
DOI: 10.16438/j.0513-4870.2018-1021
基金项目: 国家自然科学基金资助项目(81871859,81672267);大学生创新创业训练计划项目(201812121160,201812121280).
通讯作者: 张健
Email: blacktiger@139.com
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