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


METHODS
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.
Henry
Carolyn J
CJ
University of Missouri-Columbia College of Veterinary Medicine, Columbia, Missouri 65211, USA.
McCaw
Dudley L
DL
Turnquist
Susan E
SE
Tyler
Jeff W
JW
Bravo
Lina
L
Sheafor
Sarah
S
Straw
Rodney C
RC
Dernell
William S
WS
Madewell
Bruce R
BR
Jorgensen
Linda
L
Scott
Michael A
MA
Higginbotham
Mary Lynn
ML
Chun
Ruthanne
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness; D009919:Orchiectomy; D010052:Ovariectomy; D010894:Piroxicam / Q000627:therapeutic use*; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality
D000970:Antineoplastic Agents; D010894:Piroxicam; D008942:Mitoxantrone