Renal Injury during Long-Term Crizotinib Therapy

Int J Mol Sci. 2018 Sep 25;19(10):2902. doi: 10.3390/ijms19102902.

Abstract

Crizotinib is highly effective against anaplastic lymphoma kinase-positive and c-ros oncogen1-positive non-small cell lung cancer. Renal dysfunction is associated with crizotinib therapy but the mechanism is unknown. Here, we report a case of anaplastic lymphoma kinase positive non-small cell lung cancer showing multiple cysts and dysfunction of the kidneys during crizotinib administration. We also present results demonstrating that long-term crizotinib treatment induces fibrosis and dysfunction of the kidneys by activating the tumor necrosis factor-α/nuclear factor-κB signaling pathway. In conclusion, this study shows the renal detrimental effects of crizotinib, suggesting the need of careful monitoring of renal function during crizotinib therapy.

Keywords: anaplastic lymphoma kinase; crizotinib; cystic formation; fibrosis; lung cancer; renal injury.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Crizotinib / adverse effects*
  • Crizotinib / therapeutic use
  • Female
  • Fibrosis
  • Humans
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology
  • Kidney Diseases, Cystic / chemically induced*
  • Kidney Diseases, Cystic / pathology
  • Kidney Diseases, Cystic / physiopathology
  • Lung Neoplasms / drug therapy*
  • Mice

Substances

  • Antineoplastic Agents
  • Crizotinib