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

Aim: 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.

Material And Method: 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.

Results: 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.

Conclusion: 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.