title: ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice?
abstract: Crizotinib (XALKORI™, Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer. Optimizing the management of frequent crizotinib-related adverse events is crucial to ensure its continuous administration and reproduce the response and survival rates reported in clinical trials. Here, we propose some practical measures, which are mostly derived from the recommendations given to the investigators of the PROFILE 1001, 1005, 1007 and 1014 trials and are based on experience and scientific findings regarding the management of these disorders. While visual disturbances or bradycardia are frequent but benign, the severity of the cardiac and hepatic adverse events requires special attention potential to QT interval prolongations and to the monitoring of electrolyte levels and liver function, taking into account potential drug-drug interactions.
authors.affiliation: Department of Respiratory Medicine and Thoracic Oncology, Hôpital Louis Pradel, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.forename: Clarisse
authors.initials: C
authors.lastname: Audigier-Valette
authors.forename: Alexis B
authors.initials: AB
authors.lastname: Cortot
authors.forename: Bertrand
authors.initials: B
authors.lastname: Mennecier
authors.forename: Didier
authors.initials: D
authors.lastname: Debieuvre
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.forename: Denis
authors.initials: D
authors.lastname: Moro-Sibilot
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlési
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077547:Crizotinib; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; 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*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; crizotinib; drug safety; heart; liver; lung cancer