title: Crizotinib-induced fatal fulminant liver failure.
abstract: Herein we describe a case of a 62-year-old female in good clinical condition with non-small-cell lung cancer who was treated with crizotinib. After 24 days of crizotinib therapy she presented with acute liver failure. Serum aspartate aminotransferase and alanine aminotransferase levels had increased from normal prior to crizotinib start to 2053 IU/L and 6194 IU/L, respectively. Total bilirubin and prothrombin time (PT-INR) increased up to 443 IU/L and 5.33, respectively, and symptoms of hepatic encephalopathy and hepatorenal syndrome emerged. Despite crizotinib discontinuation and intensive supportive therapy, the patient died 40 days after treatment with crizotinib was initiated due to acute liver failure with massive liver cell necrosis.
authors.affiliation: Department of Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: r.v.geel@nki.nl.
authors.forename: Robin M J M
authors.initials: RM
authors.lastname: van Geel
authors.affiliation: Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jeroen J M A
authors.initials: JJ
authors.lastname: Hendrikx
authors.affiliation: Department of Pulmonology, Haga Teaching Hospital, The Hague, The Netherlands.
authors.forename: Jelmer E
authors.initials: JE
authors.lastname: Vahl
authors.affiliation: Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Monique E
authors.initials: ME
authors.lastname: van Leerdam
authors.affiliation: Department of Clinical Chemistry, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: van den Broek
authors.affiliation: Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
authors.affiliation: Department of Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.affiliation: Department of Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.affiliation: Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sjaak A
authors.initials: SA
authors.lastname: Burgers
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis*; D000077547:Crizotinib; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000175:diagnosis*; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy; D008875:Middle Aged; 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
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib
keywords: Crizotinib; Fulminant liver failure; Hepatotoxicity; Non-small cell lung cancer