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Drug Saf. 2019 Feb;42(2):199-209. doi: 10.1007/s40264-018-0771-y.

Safety and Tolerability of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer.

Author information

1
Division of Pulmonary Oncology, Azienda Ospedaliera Dei Colli Monaldi, Naples, Italy.
2
"Luigi Vanvitelli" University, Caserta, Italy.
3
Division of Medical Oncology, "S.G. Moscati" Hospital, Contrada Amoretta, 83100, Avellino, Italy. cgridelli@libero.it.

Abstract

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.

PMID:
30649741
DOI:
10.1007/s40264-018-0771-y

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