Xalkori

Xalkori is the brand name for crizotinib, an oral small-molecule tyrosine kinase inhibitor used in cancer therapy. It targets abnormal kinases produced by gene rearrangements, most notably anaplastic lymphoma kinase (ALK) and ROS1, and to a lesser extent MET. By inhibiting these kinases, crizotinib blocks signaling pathways that promote tumor cell growth and survival in tumors driven by ALK or ROS1 alterations.

Medical uses for crizotinib include metastatic non-small cell lung cancer (NSCLC) that tests positive for ALK rearrangements and NSCLC with ROS1 rearrangements. In some settings, crizotinib has been studied or approved for other ALK- or ROS1-driven cancers under specific indications. The utility of crizotinib depends on selecting patients whose tumors harbor the target genetic alterations.

Administration and pharmacology: Crizotinib is taken by mouth, commonly at a dose of 250 mg twice daily, with or without food (dosing may vary by indication and region). It is primarily metabolized in the liver by the cytochrome P450 3A4 enzyme and has a relatively long terminal half-life. Because of CYP3A involvement, strong inhibitors or inducers can markedly affect crizotinib levels, and careful consideration of drug interactions is recommended. Crizotinib can have effects on the QT interval, so monitoring may be required in some patients.

Safety and monitoring: Common adverse effects include vision disturbances, nausea, vomiting, diarrhea, edema, and fatigue. Serious risks include hepatotoxicity, interstitial lung disease or pneumonitis, QT prolongation or bradycardia, and neutropenia. Baseline and periodic monitoring of liver function tests, as well as assessment for respiratory symptoms and, when appropriate, electrocardiographic monitoring, are typically advised.

Development and regulatory status: Crizotinib was developed by Pfizer as a first-in-class ALK and ROS1 inhibitor for NSCLC, with subsequent approvals expanding to ROS1-rearranged NSCLC and related indications in various countries.