Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma.

PURPOSE Cyclooxygenase inhibitors show promise in chemoprevention and therapy of certain carcinomas, an effect that may be additive to that of standard chemotherapy. The purpose of this study was to evaluate the efficacy of combined therapy using the cyclooxygenase inhibitor, piroxicam, and mitoxantrone against a relevant canine model of human invasive bladder cancer. EXPERIMENTAL DESIGN Fifty-five dogs with transitional cell carcinoma of the urinary bladder were enrolled in this nonrandomized one-armed prospective multi-institutional clinical trial. Mitoxantrone was administered i.v. (5 mg/m(2)) every 21 days for four treatments, and piroxicam was administered p.o. (0.3 mg/kg/day) for the study duration. Tumor staging was performed at baseline, day 42 and every 3 months after protocol completion. Endpoints included time-to-treatment failure and survival time (ST). RESULTS Response data were available for 48 dogs and included one complete response, 16 partial responses, 22 with disease stabilization, and 9 with progressive disease for an overall 35.4% measurable response rate. Subjective improvement occurred in 75% of treated dogs. Median time-to-treatment failure and ST were 194 and 350 days, respectively. Using censoring and end point definitions similar to those of previous reports of dogs treated with piroxicam alone, the median ST in this study was 291 days, compared with 181 days with piroxicam alone. Diarrhea and azotemia were the most common treatment complications. CONCLUSIONS Mitoxantrone/piroxicam induced remission more frequently than previously reported for either drug as a single agent in this canine model of invasive human transitional cell carcinoma. Additional evaluation of these drugs in combination protocols should be explored.