Renal effects of high-dose celecoxib in elderly men with Stage D2 prostate carcinoma

Abstract

To prospectively study the clinical renal effects of daily high-dose celecoxib, a COX-2 inhibitor, in a cohort of elderly sick men (mean age 74.5 years) with advanced prostate cancer. 44 men with advanced hormoneresistant prostate cancer participated in oncologic Phase II trials. All received celecoxib 400 mg bid for a median 6 months. Monthly laboratory measurement and blood pressure were monitored, and all cases of acute kidney injury (creatinine > 50% above baseline) and hyperkalemia (potassium > 5.5 mmol/l) were evaluated. Mean chemistries, BP, and estimated GFR (e-GFR) during treatment were compared to 6-month periods before and after treatment. There was no change in e-GFR (pre, 78.1 ± 22 ml/min; during treatment, 76 ± 19 ml/min). Serum K rose (4.25 ± 0.4 mmol/l to 4.39 ± 0.3 mmol/l, p = 0.03), and bicarbonate fell (28.16 ± 0.2 to 26.18 ± 0.2 mmol/l, p < 0.01) with treatment. 15% of patients developed AKI, close to the incidence of AKI episodes in the pre- (9%) and post-treatment periods (13%). AKI was mild, short-lived, and reversible, except in a terminal patient who withdrew. All AKI occurred in states of renal hypoperfusion, and were not related to celecoxib alone. Hyperkalemia developed in 9% of patients. No patient developed new-onset proteinuria. High-dose celecoxib for 6 months was relatively well tolerated. e-GFR remained stable and there were minor electrolyte alterations. Although the AKI incidence was much higher than other studies, it was not much higher than in the pre- and post-treatment periods (high "background noise"). All AKI occurred in states of renal hypoperfusion, not unexpected for prostaglandin inhibitors.