Drug-induced reduction in estimated glomerular filtration rate in patients with ALK-positive non-small cell lung cancer treated with the ALK inhibitor crizotinib

Authors

  • Evelyn M. Brosnan MD, BS, MBA,

    1. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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  • Andrew J. Weickhardt MBBS, DMedSc,

    1. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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  • Xian Lu MSc,

    1. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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  • Delee A. Maxon BS,

    1. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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  • Anna E. Barón PhD,

    1. Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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  • Michel Chonchol MD,

    1. Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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  • D. Ross Camidge MD, PhD

    Corresponding author
    1. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
    • Corresponding author: D. Ross Camidge, MD, PhD, Division of Medical Oncology, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, 1665 North Aurora Ct, Room ACP 5327, Aurora, CO 80045; Fax: (720) 848-0536; ross.camidge@ucdenver.edu

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  • This study was successfully submitted as part of Dr. Brosnan's Capstone-mentored scholarly activity research project during her medical school education at the University of Colorado in Denver. Dr. Brosnan gratefully acknowledges the additional support and contributions of Dr. Jean Abbott, Lynne Fox, Dr. Rita Lee, and Dr. Stuart Linas to this project.

Abstract

BACKGROUND

To the best of the authors' knowledge, the renal side effects of crizotinib have not been investigated previously.

METHODS

The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based prediction equation during the first 12 weeks of crizotinib therapy and after crizotinib but before the introduction of any further systemic therapy.

RESULTS

A total of 38 patients with stage IV anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer who were treated with crizotinib were identified. The mean eGFR decreased by 23.9% compared with baseline (P < .0001; 95% confidence interval, 21.3%-26.6%), with the majority of the decrease occurring within the first 2 weeks of therapy. Clinical history and blood urea nitrogen/creatinine ratios did not suggest prerenal causes. The objective response rate among evaluable patients (n = 27) was 41%. Tumor shrinkage was not correlated with changes in eGFR (correlation coefficient, −0.052; P = .798). Among the 16 patients for whom data after treatment with crizotinib were available, recovery to within 84% of the baseline eGFR occurred in all patients. After adjusting for the number of scans with intravenous contrast and the use of known nephrotoxic drugs, the issue of whether a patient was on or off crizotinib treatment was found to be significantly associated with changes in eGFR (P < .0001).

CONCLUSIONS

As assessed by the Chronic Kidney Disease Epidemiology Collaboration prediction equation, eGFR is reduced by treatment with crizotinib, but the majority of patients will recover their eGFR after the cessation of therapy. The early onset, size of the change, minimal cumulative effect, and rapid reversibility raise the possibility that this may be a pharmacological and/or tubular creatinine secretion effect rather than a direct nephrotoxic effect. Increased vigilance with regard to the concomitant use of renally cleared medications or nephrotoxic agents should be considered for patients receiving crizotinib and, when eGFR is reduced, additional renal investigations should be undertaken. Cancer 2014;120:664–674. © 2013 American Cancer Society.

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