Crizotinib

摘要: Crizotinib (Xalkori, Pfizer) is an aminopyridine tyrosine kinase inhibitor active against RON, as well ALK, MET, ROS1, and some of their oncogenic variants. It was initially developed a second-generation selective MET through modification previous molecule (PHA-665,752) before the identification EML4-ALK translocation in non–small-cell lung cancer (NSCLC), then found to be highly anaplastic lymphoma (ALK) inhibitor. The Food Drug Administration (FDA) granted accelerated approval 2011 for use crizotinib patients with locally advanced or metastatic ALK-positive NSCLC, detected by FDA-approved test (FISH probe kit). European Medicines Agency (EMA) conditional 2012 its adults previously treated NSCLC. Moreover, EMA did not request specific diagnostic ALK rearrangements. safety database at consisted 340 subjects who had received least one dose crizotinib, including 255 ALK-positive, advanced, NSCLC standard 250 mg/bid, therefore represented core population detailed adverse event evaluation. By March 2015, accounted 1200 NCSLC continuous monotherapy recommended starting dose. Most common toxicities include visual, gastrointestinal, constitutional disorders, followed cardiovascular, respiratory, minor neurologic dysfunctions. More concerning events severe hepatotoxicity, interstitial disease/pneumonitis, bradycardia, QT prolongation.