Resolution of Crizotinib-Associated Fulminant Hepatitis following Cessation of Treatment

Case Reports in Hepatology
Gregory W CharvillePaul Y Kwo

Abstract

Targeted cancer treatments offer the prospect of precise inhibition of tumor growth without the untoward off-target toxicity of traditional chemotherapies. Still, unintended, often idiosyncratic side effects, such as drug-induced liver injury, can occur. We discuss the case of a 26-year-old female with a history of ROS1-rearranged lung adenocarcinoma, undergoing treatment with the tyrosine kinase inhibitor crizotinib, who presented to our hospital with abdominal pain and scleral icterus. Liver chemistries were notable for hyperbilirubinemia (5 mg/dL total) and marked transaminasemia (AST 1736 U/L, ALT >3500 U/L); liver biopsy demonstrated acute hepatitis with extensive necrosis. There was no evidence of an infectious or autoimmune etiology. It was discovered that the patient was taking a 500 mg once daily dose of crizotinib, in lieu of the intended dose of 250 mg twice daily. After immediate cessation of crizotinib therapy upon hospital admission, there was complete biochemical resolution of the hepatitis. This case highlights the potential reversibility of fulminant crizotinib-associated hepatoxicity, possibly related to supratherapeutic dosing, when managed with abrupt stoppage of the drug and initiation of supportive care.

References

Oct 29, 2010·The New England Journal of Medicine·Eunice L KwakA John Iafrate
Nov 28, 2012·Clinics and Research in Hepatology and Gastroenterology·Marie-Pierre RipaultDominique Larrey
Jun 27, 2014·Japanese Journal of Clinical Oncology·Yuki SatoKeisuke Tomii
Sep 30, 2014·The New England Journal of Medicine·Alice T ShawA John Iafrate
Dec 4, 2014·The New England Journal of Medicine·Benjamin J SolomonUNKNOWN PROFILE 1014 Investigators
Mar 11, 2015·Gastroenterology·Naga ChalasaniUNKNOWN United States Drug Induced Liver Injury Network
Feb 24, 2016·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Robin M J M van GeelSjaak A Burgers

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Methods Mentioned

BETA
biopsy
PCR

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