title: [ALK-rearranged non-small cell lung cancer: how to optimize treatment with crizotinib in routine practice?].
abstract: Crizotinib (XALKORI(™), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer. This work from an expert group, based on the review of the data from the Profile studies, aims to provide practical elements in order to optimize the tolerability of crizotinib. Specific major or frequent side effects of crizotinib are discussed: visual disturbances, cardiac effects, elevated transaminases, and hypogonadism. In the routine practice, patients should be advised about visual disturbances, especially with regard to driving in low brightness. Digestive disorders related to crizotinib are exceptionally persistent or severe. Dietary measures and symptomatic treatments usually control these disorders. It is recommended to perform an electrocardiogram before introduction of crizotinib, to identify prolonged QT interval. Torsades de pointes may produce dizziness or syncope. Hypogonadism should be considered in case of fatigue, decreased libido, and even depression, taking into account that these symptoms may be related to cancer; testosterone serum level should be measured to identify patients that may be eligible to receive a supplementation. Monitoring of liver function tests, including transaminases and bilirubin, is necessary. To conclude, these practical elements are helpful to optimize treatment with crizotinib in patients with ALK-rearranged lung cancer; in the future, academic initiatives should be taken to study these aspects, based on the monitoring of large cohorts of patients treated with crizotinib.
authors.affiliation: CHITS Toulon, Hôpital de Toulon, Service de pneumologie, 54, rue Sainte-Claire-Deville, 83056 Toulon, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Audigier-Valette
authors.affiliation: Université Claude-Bernard Lyon 1, Hospices civils de Lyon, Hôpital Louis-Pradel, Service de pneumologie, 69677 Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.affiliation: Université Lille Nord de France, CHRU de Lille, Service de pneumologie et oncologie thoracique, 59000 Lille, France.
authors.forename: Alexis B
authors.initials: AB
authors.lastname: Cortot
authors.affiliation: Nouvel Hôpital civil, Service de pneumologie, 67091 Strasbourg, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Mennecier
authors.affiliation: Hôpital de Mulhouse, Service de pneumologie, 68100 Mulhouse, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Debieuvre
authors.affiliation: Gustave-Roussy, Service d'oncologie médicale, 94805 Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.affiliation: CHU Côte-de-Nacre, Service de pneumologie et oncologie thoracique, 14033 Caen, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.affiliation: CHRU de Grenoble, Hôpital Michallon, Service de pneumologie, 38043 Grenoble, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Moro-Sibilot
authors.affiliation: AP-HP, Hôpital Tenon, Service de pneumologie et Sorbonne Universités, UPMC Univ 75006 Paris 06 - GRC n̊ 04, Theranoscan 75970 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.affiliation: AP-HP Marseille, Université Aix-Marseille, Service d'oncologie multidisciplinaire & innovations thérapeutiques, 13015 Marseille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D000077547:Crizotinib; D004066:Digestive System Diseases / Q000139:chemically induced; D015321:Gene Rearrangement; D006801:Humans; D007006:Hypogonadism / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010353:Patient Education as Topic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D016171:Torsades de Pointes / Q000139:chemically induced; D014786:Vision Disorders / Q000139:chemically induced
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: anaplastic lymphoma kinase; crizotinib; lung cancer; side effects; tolerance