Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC |
| |
Authors: | D Ross Camidge Elizabeth E Kim Tiziana Usari Anna Polli Iona Lewis Keith D Wilner |
| |
Institution: | 1. University of Colorado Comprehensive Cancer Center, Aurora, Colorado;2. Pfizer, Inc., New York, New York;3. Pfizer Oncology, Milan, Italy;4. Pfizer, Inc., Collegeville, Pennsylvania;5. Pfizer Oncology, La Jolla, California |
| |
Abstract: | IntroductionWe 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).MethodsChanges 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.ResultsMedian 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.ConclusionsCrizotinib 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: | Corresponding author Address for correspondence: D Ross Camidge MD PhD University of Colorado Comprehensive Cancer Center 1665 Aurora Ct Aurora Colorado 80045 Crizotinib ALK receptor tyrosine kinase NSCLC Renal function Estimated glomerular filtration rate |
本文献已被 ScienceDirect 等数据库收录! |
|