Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC

J Thorac Oncol. 2019 Jun;14(6):1077-1085. doi: 10.1016/j.jtho.2019.02.015. Epub 2019 Feb 26.


Introduction: We retrospectively analyzed the effects of crizotinib on serum creatinine and creatinine-based estimated glomerular filtration rate (eGFR) in patients with anaplastic lymphoma kinase-positive advanced NSCLC across four trials (NCT00585195, NCT00932451, NCT00932893, and NCT01154140).

Methods: Changes from baseline data in serum creatinine and eGFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation, were assessed over time. eGFR was graded using standard chronic kidney disease criteria.

Results: Median serum creatinine increased from 0.79 mg/dL at baseline to 0.93 mg/dL after 2 weeks of treatment (median percentage increase from baseline, 21.2%), was stable from week 12 (0.96 mg/dL) to week 104 (1.00 mg/dL), and decreased to 0.90 mg/dL at 28 days after last dose (median percentage increase from baseline, 13.1%). Median eGFR decreased over time (96.42, 80.23, 78.06 and 75.45 mL/min/1.73 m2 at baseline, week 2, week 12, and week 104, respectively) and increased to 83.02 mL/min/1.73 m2 at 28 days after the last dose. Median percentage decrease from baseline was 14.9%, 17.0%, and 10.4% at week 2, week 12, and 28 days after last dose of crizotinib, respectively. Overall, 12.6% of patients had a shift from eGFR grade less than or equal to 3a (≥45 mL/min/1.73 m2) at baseline to greater than or equal to 3b (<45 mL/min/1.73 m2) post-baseline.

Conclusions: Crizotinib resulted in a decline in creatinine-based estimates of renal function mostly over the first 2 weeks of treatment. However, there was minimal evidence of cumulative effects with prolonged treatment and these changes were largely reversible following treatment discontinuation, consistent with previous reports suggesting this may be predominantly an effect on creatinine secretion as opposed to true nephrotoxicity.

Keywords: ALK receptor tyrosine kinase; Crizotinib; Estimated glomerular filtration rate; NSCLC; Renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Creatinine / blood
  • Crizotinib / pharmacology*
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Kidney / drug effects*
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Male
  • Protein Kinase Inhibitors / pharmacology*
  • Retrospective Studies


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Crizotinib
  • Creatinine
  • ALK protein, human
  • Anaplastic Lymphoma Kinase

Associated data