Effects of cyclooxygenase inhibitor treatment on the renal toxicity of cisplatin in rats.

PURPOSE: The purpose of this study was to determine the effects of a nonselective cyclooxygenase (cox) inhibitor and of a selective cox-2 inhibitor on the renal toxicity of cisplatin. METHODS: Cisplatin with or without a cox-1 inhibitor (SC560), a cox-2 inhibitor (SC236), or a nonselective cox inhibitor (piroxicam) was administered to Sprague-Dawley rats. Renal toxicity was assessed by serum creatinine concentration (SCR), urine specific gravity (USG), and histopathologic lesion score (HLS). RESULTS: Acutely, the SCR was significantly higher in rats receiving cisplatin/SC560 (1.62+/-0.34 mg/dl) or cisplatin/piroxicam (2.0+/-0.41 mg/dl) than in rats receiving cisplatin alone (1.09+/-0.40 mg/dl). The apparent increase in SCR in the rats receiving cisplatin/SC236 (1.58+/-0.31) was not significantly different from that of rats receiving cisplatin alone (1.09+/-0.40 mg/dl). No significant differences in USG or HLSs were noted between rats receiving cisplatin alone and cisplatin combined with any cox inhibitor. In a chronic study, no differences in renal toxicity were found between rats treated with cisplatin alone and cisplatin/SC236 or cisplatin/piroxicam. CONCLUSIONS: The acute rise in SCR following cisplatin treatment can be worsened by the addition of cox inhibitors, especially those that inhibit cox-1.

Evaluation of cisplatin administered with piroxicam in dogs with transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To evaluate the antitumor activity and toxic effects of a conservative dose of cisplatin administered in combination with piroxicam to dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN: Clinical trial (nonrandomized, noncontrolled). ANIMALS: 14 client-owned dogs with histologically confirmed TCC of the urinary bladder. PROCEDURES: Each dog was treated with cisplatin (50 mg/m(2), i.v., q 21 d [reduced to 40 mg/m(2), i.v., q 21 d because of toxic effects]) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). A CBC, serum biochemical analyses, and urinalysis were performed prior to each cisplatin treatment. Tumor staging (determined from thoracic and abdominal radiographic and urinary bladder ultrasonographic findings) was performed before treatment and at 6-week intervals during treatment. RESULTS: 5 dogs received only 1 dose of cisplatin because of the rapid progression of disease (n = 2) or toxic effects (3). With regard to the neoplastic disease among the other 9 dogs, 1 had partial remission, 5 had stable disease, and 3 had progressive disease after 6 weeks of treatment. Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m(2)) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder.