Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). Crizotinib inhibits the c-Met/Hepatocyte growth factor receptor (HGFR) tyrosine kinase, which is involved in the oncogenesis of a number of other histological forms of malignant neoplasms. It also acts as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor.
Read the full article on WikipediaStage IIIB (locally advanced) or Stage IV (metastatic) non-small cell lung cancer (NSCLC) Clinical criteria: Treatment Phase: Initial treatment The treatment must be the sole PBS-subsidised systemic anti-cancer therapy for this condition, AND The condition must be non-squamous type non-small cell lung cancer (NSCLC) or not otherwise specified type NSCLC, AND Patient must have a WHO performance status of 2 or less, AND Patient must have evidence of an anaplastic lymphoma kinase (ALK) gene rearrangement in tumour material, defined as either: (i) 15% (or greater) positive cells by fluorescence in situ hybridisation (FISH) testing, (ii) positive next generation sequencing (NGS) testing. Treatment criteria: Must be treated by a medical practitioner. Applications for authorisation of initial treatment must be made via the Online PBS Authorities System (real time assessment) or in writing via HPOS form upload or mail. If the application is submitted through HPOS form upload or mail, it must include: (a) details of the proposed prescription; and (b) a completed authority application form relevant to the indication and treatment phase (the latest version is located on the website specified in the Administrative Advice). The following must be documented in the patient's medical records: (a) evidence of an anaplastic lymphoma kinase (ALK) gene rearrangement in tumour material.
“Crizotinib has an aminopyridine structure, and functions as a protein kinase inhibitor by competitive binding within the ATP-binding pocket of target kinases. About 4% of patients with non-small cell lung carcinoma have a chromosomal rearrangement that generates a fusion gene between EML4 ('echinoderm microtubule-associated protein-like 4') and ALK ('anaplastic lymphoma kinase'), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotype. The kinase activity of the fusion protein is inhibited by crizotinib. Patients with this gene fusion are typically younger non-smokers who do not have mutations in either the epidermal growth factor receptor gene (EGFR) or in the K-Ras gene. The number of new cases of ALK-fusion NSLC is about 9,000 per year in the U.S. and about 45,000 worldwide.”
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