title: A safety assessment of crizotinib in the treatment of ALK-positive NSCLC patients.
abstract: BACKGROUND
  In the past decade, the treatment of NSCLC has been revolutionized by the discovery of key oncogenic driver mutations and the therapies that specifically target these mutations. Crizotinib has been shown to be an inhibitor of MET, anaplastic lymphoma kinase (ALK) and ROS1 receptor tyrosine kinases, and is FDA approved for ALK inhibition. Crizotinib is effective in NSCLC that harbors ALK translocations resulting in overexpression of oncogenic ALK fusion proteins.
  
  
  METHODS
  This paper will review crizotinib as a treatment for ALK-positive NSCLC. It will discuss the drug's adverse events, drug-drug interactions and other important clinical and safety information related to crizotinib.
  
  
  CONCLUSIONS
  Compared to standard chemotherapy, crizotinib shows improved progression-free survival in ALK-positive NSCLC, with patient's reporting improved quality of life. However, certain adverse events are more frequent with crizotinib versus standard chemotherapy and must be monitored for closely. The most common adverse events include ocular and gastrointestinal disturbances, cardiac and endocrine abnormalities, and peripheral edema. Many, though not all, of these side effects are likely due to the multiple tyrosine kinases inhibited by crizotinib, and will likely improve with second- and third-generation inhibitors that inhibit ALK more specifically.
authors: The University of Chicago Medicine, University of Chicago Medical Center , 5481 S. Maryland Ave, Chicago, IL 60637 , USA +1 773 702 4399 ; +1 773 834 1798 ; rsalgia@medicine.bsd.uchicago.edu.
authors: Alana
authors: A
authors: Dikopf
authors: Kevin
authors: K
authors: Wood
authors: Ravi
authors: R
authors: Salgia
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000077547:Crizotinib; D004347:Drug Interactions; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D011788:Quality of Life; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: NSCLC; adverse effects; anaplastic lymphoma kinase; crizotinib; drug safety; lung cancer