Fulminant hepatitis following crizotinib administration for ALK-positive non-small-cell lung carcinoma

Jpn J Clin Oncol. 2014 Sep;44(9):872-5. doi: 10.1093/jjco/hyu086. Epub 2014 Jun 25.

Abstract

We herein report a case of fatal fulminant hepatitis secondary to crizotinib administration. The patient was 54-year-old female with a history of Hepatitis C infection (not current), dermatomyositis and steroid-induced diabetes mellitus. She was diagnosed with advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement. We began 400 mg of crizotinib as first-line therapy. No adverse effects were seen until Day 16. On Day 29, she was admitted to hospital with elevated liver enzymes (aspartate aminotransferase 3236 IU/l, alanine aminotransferase 5201 IU/l) and coagulopathy (prothrombin time <10%), and was diagnosed with crizotinib-induced fulminant hepatitis. We started intensive care, using plasma exchange, continuous hemodiafiltration and high-dose steroid therapy. Unfortunately, she did not respond to therapies, and died on Day 36. The mechanism and risk factors of crizotinib-induced hepatotoxicity are uncertain. Physicians should be aware of possible adverse effects of crizotinib. A systemic survey is imperative to identify possible risk factors of crizotinib-related hepatotoxicity.

Keywords: anaplastic lymphoma kinase; crizotinib; drug induced liver toxicity; fulminant hepatitis; tyrosine kinase inhibitor.

Publication types

  • Case Reports

MeSH terms

  • Alanine Transaminase / blood
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Aspartate Aminotransferases / blood
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Chemical and Drug Induced Liver Injury / enzymology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / therapy
  • Crizotinib
  • Fatal Outcome
  • Female
  • Humans
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / drug therapy*
  • Middle Aged
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Receptor Protein-Tyrosine Kinases / analysis*
  • Risk Factors

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases