ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice?

Expert Rev Anticancer Ther. 2015 Feb;15(2):225-33. doi: 10.1586/14737140.2014.986103. Epub 2014 Nov 21.

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.

Keywords: ALK; crizotinib; drug safety; heart; liver; lung cancer.

Publication types

  • Review

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib
  • Drug Interactions
  • Drug Monitoring / methods
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Survival Rate

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases