Reduced Renal Function Observed in Patients Taking Crizotinib for Non‒Small Cell Lung Cancer
Patients receiving crizotinib (Xalkori) for the treatment of anaplastic lymphoma kinase (ALK)-positive non?small cell lung cancer (NSCLC) had reductions in their estimated glomerular filtration rate, according to the findings of a study by Brosnan et al published in the journal Cancer. In the majority of patients, complete recovery in the estimated glomerular filtration rate was attained upon cessation of crizotinib therapy.
Crizotinib Associated With Renal Adverse Effects
Crizotinib, a small-molecule ALK inhibitor, has been successfully utilized by health-care professionals for the treatment of ALK-positive NSCLC. Although crizotinib is associated with some adverse effects, one in particular, renal side effects, may be of concern. With that in mind, Brosnan et al analyzed the possible effect of crizotinib-associated renal side effects on patients with ALK?positive non?small cell lung cancer.
A total of 38 patients with stage IV NSCLC took part in this study. These patients had undergone crizotinib therapy for 12 weeks. Each patient’s estimated glomerular filtration rate was compared at baseline and after 12 weeks of crizotinib therapy. The mean baseline estimated glomerular filtration rate was 82.6 mL/min/1.73 m2.
The investigators found that there was a mean 23.9% decrease in the estimated glomerular filtration rate among the 38 patients (P < .0001; 95% confidence interval [CI] = 21.3%?26.6%). The reduction was most evident in the first 2 weeks of crizotinib therapy. Any cumulative effects beyond the initial rapid reduction were found to be rare.
In order to determine that the likely reason for the decrease in the estimated glomerular filtration rate was related to crizotinib therapy, patients were evaluated for gastrointestinal concerns, emesis, diarrhea, and hypotensive blood pressure, all of which could be a factor in renal adverse effects. None of the patients experienced any significant issues related to these factors.
Patients were also evaluated for tumor lysis to determine whether that was a factor in the change in the estimated glomerular filtration rate. No correlation was noted between the percentage of tumor shrinkage and the decrease in the estimated glomerular filtration rate.
Furthermore, the investigators evaluated the relationship between the estimated glomerular filtration rate and patients who had taken time off from crizotinib therapy. It was noted that in these patients, the mean estimated glomerular filtration rate increased 18.9% over baseline (P = .047; 95% CI = 0.3%?37.4%). This recovery in the estimated glomerular filtration rate occurred in 56% of patients.
Clinical Implications
The results from this study confirm that crizotinib therapy is associated with adverse renal effects, as noted in decreases in patients’ estimated glomerular filtration rate. The investigators suggested this may be a factor in determining the appropriate length of crizotinib therapy. In addition, clinicians need to be aware of the concomitant use of known nephrotoxic or renally cleared drugs with crizotinib.
In a statement, senior author D. Ross Camidge, MD, PhD, of the University of Colorado Cancer Center, said, “The jury remains out on the exact mechanism [of crizotinib and the decrease in the estimated glomerular filtration rate]. However, because an interference with the validity of creatinine for assessing kidney function is still a possibility, if a patient’s creatinine is heading into some kind of danger zone on crizotinib, and a doctor is considering altering management of the patient, we would strongly recommend reassessing kidney function through a second, non-creatinine based method before making any final decision.”
Dr. Camidge is the corresponding author of the article in Cancer.
For full disclosures of the study authors, visit the Cancer website.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
