Efficacy and side effects of crizotinib/Xalkori

Crizotinib/Crizotinib is a tyrosine kinase receptor inhibitor mainly used to treat ALK-positive patients in non-small cell lung cancer (NSCLC). In addition, it may also be used in other types of cancer, such as anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT). Crizotinib targets anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), ROS 1 (c-ROS), and receptor d'origine Nantais (RON).

Crizotinib inhibits ALK by inhibiting its phosphorylation and producing an inactive protein conformation. This ultimately reduces the proliferation and tumor survival of cells carrying this genetic mutation. In a Phase I study, 37 patients with multiple refractory solid tumor cancers received 50 to 300 mg of crizotinib daily or twice daily. Within this group, two patients with non-small cell lung cancer (NSCLC) who exhibited echinoderm microtubule-associated protein-like 4 (EML 4)-anaplastic lymphoma kinase (ALK) mutations responded to treatment; therefore, the following study focused on patients with advanced ALK-positive disease. In this group of patients, the six-month progression-free survival rate for crizotinib users was approximately 72%. ALK mutation-positive patients who received crizotinib had a higher two-year overall survival rate compared with those who did not receive crizotinib (54% vs. 36%).

In pediatric and young adult patients with anaplastic large cell lymphoma (ALCL) or pediatric patients with inflammatory myofibroblastic tumor (IMT), use of crizotinib may result in hepatotoxicity, interstitial lung disease (ILD), pneumonitis, QT prolongation, bradycardia, severe vision loss, embryo-fetal toxicity, and gastrointestinal toxicity.