"Bladder Cancer Update" TUMOR TIDBITS, A BIWEEKLY EMAIL NEWSLETTER FROM GULF COAST VETERINARY ONCOLOGY Number 90; February 28, 2003. ======================================================================= THIS WEEK'S TUMOR TIDBIT: Bladder Cancer Update ======================================================================= Spring is almost here and March 15th is our Second Annual Patient Celebration in Houston - all are welcome. Contact Ms. Julie Ormond for additional details (713.693.1166). Visit our web site for other exciting information. ======================================================================= When is the last time you read the Journal of Clinical Cancer Research? We'll it's a great journal for the latest and greatest in comparative medicine and the recent issue reported the findings of a study evaluating Mitoxantrone and Piroxicam therapy for dogs with bladder cancer. This is a protocol we have used at Gulf Coast Veterinary Oncology (along with radiation therapy) for a number of years so we were glad to see the report. In short, 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 canine invasive bladder cancer. 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 PO (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). Forty-eight dogs were evaluated with 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 survival curve estimations, 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. In conclusion, mitoxantrone/piroxicam induced remission more frequently than previously reported for either drug as a single agent. WHAT DO WE DO AT GULF COAST VETERINARY ONCOLOGY? Our best protocol for managing bladder cancer in dogs is to consider the use of piroxicam (orally once daily as above), Mitoxantrone (every 2 weeks for 3 times), and irradiation of the urinary bladder, urethra and associated nodes (every 2 weeks for 3 times on the same day as Mitoxantrone chemotherapy) with results similar to slightly improved compared to those reported by Drs. Henry and others in Clinical Cancer Research. In general, we anticipate a 40-50% overall remission response (tumor shrinkage and improvement of clinical signs) with a duration of good quality life ranging from 6 to 22 months (median 18 months). SUGGESTED READING Henry CJ, McCaw DL, Turnquist SE, Tyler JW, Bravo L, Sheafor S, Straw RC, Dernell WS, Madewell BR, Jorgensen L, Scott MA, Higginbotham ML, Chun R. Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma. Clin Cancer Res 2003 Feb;9(2):906-11 Mohammed SI, Craig BA, Mutsaers AJ, Glickman NW, Snyder PW, DeGortari AE, Schlittler DL, Coffman KT, Bonney PL, Knapp DW. Effects of the Cyclooxygenase Inhibitor, Piroxicam, in Combination with Chemotherapy on Tumor Response, Apoptosis, and Angiogenesis in a Canine Model of Human Invasive Urinary Bladder Cancer. Mol Cancer Ther 2003 Feb;2(2):183-188 Knapp DW, Glickman NW, Widmer WR, DeNicola DB, Adams LG, Kuczek T, Bonney PL, DeGortari AE, Han C, Glickman LT. Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer Chemother Pharmacol 2000;46(3):221-6 Knapp DW, Chan TC, Kuczek T, Reagan WJ, Park B. Evaluation of in vitro cytotoxicity of nonsteroidal anti-inflammatory drugs against canine tumor cells. Am J Vet Res 1995 Jun;56(6):801-5 Knapp DW, Richardson RC, Bottoms GD, Teclaw R, Chan TC. Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors. Cancer Chemother Pharmacol 1992;29(3):214-8 ======================================================================= As always, we hope this info helps and don't hesitate to call or email us Gulf Coast Veterinary Oncology! Kevin A. Hahn, DVM, PhD, Diplomate ACVIM (Oncology), drhahn@gcvs.com Janet K. Carreras, VMD, Diplomate ACVIM (Oncology), drcarreras@gcvs.com Glen K. King, DVM, MS, Diplomate ACVR (Radiology & Radiation Therapy), drking@gcvs.com Gulf Coast Veterinary Diagnostic Imaging & Oncology 1111 West Loop South, Suite 150, Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 W: www.gcvs.com