Division of Pulmonary Oncology, Azienda Ospedaliera Dei Colli Monaldi, Naples, Italy.
"Luigi Vanvitelli" University, Caserta, Italy.
Drug Saf. 2019 Feb;42(2):199-209. doi: 10.1007/s40264-018-0771-y.
The chimeric protein echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, resulting from the rearrangement of the homonym genes, is one of the currently targetable oncogenic drivers in anaplastic lymphoma kinase-positive non-small-cell lung cancer. In fact, four first- and second-generation anaplastic lymphoma kinase tyrosine kinase inhibitors, crizotinib (PF-02341066), ceritinib (LDK378), alectinib (CH5424802), and brigatinib (AP26113), are presently approved for clinical practice; however, these agents are not devoid of complications and thus should be administered meaningfully. Furthermore, third-generation inhibitors are currently under development to overcome acquired resistance mechanisms inevitably resulting from treatment with first- and second-generation tyrosine kinase inhibitors. Therefore, this article aims to provide a comprehensive state-of-the-art review about the pharmacodynamics, pharmacokinetics, safety, and tolerability profiles of currently available and promising under-development anaplastic lymphoma kinase tyrosine kinase inhibitors.
嵌合蛋白棘皮动物微管相关蛋白样 4-间变性淋巴瘤激酶，由同源基因重排产生，是间变性淋巴瘤激酶阳性非小细胞肺癌中目前可靶向的致癌驱动基因之一。事实上，目前已有四种第一代和第二代间变性淋巴瘤激酶酪氨酸激酶抑制剂，克唑替尼（PF-02341066）、色瑞替尼（LDK378）、阿来替尼（CH5424802）和布加替尼（AP26113），被批准用于临床实践；然而，这些药物并非没有并发症，因此应该合理使用。此外，目前正在开发第三代抑制剂以克服第一代和第二代酪氨酸激酶抑制剂治疗不可避免产生的获得性耐药机制。因此，本文旨在全面介绍目前可用和有前途的间变性淋巴瘤激酶酪氨酸激酶抑制剂的药效学、药代动力学、安全性和耐受性特征。
