Phase I clinical trial and pharmacokinetics of intravesical mitomycin C in dogs with localized transitional cell carcinoma of the urinary bladder.
BACKGROUND
Transitional cell carcinoma (TCC) is the most common cancer of the urinary tract in dogs. The most frequent cause of death is urinary obstruction from the primary tumor. Standard medical therapy for TCC is only partially effective.


OBJECTIVE
Intravesical administration of mitomycin C (MMC) in dogs with invasive TCC will result in antitumor activity against the primary tumor and minimal systemic drug absorption.


METHODS
Thirteen privately owned dogs with naturally occurring, histopathologically diagnosed TCC of the urinary bladder.


METHODS
A prospective phase I trial was performed. MMC was given intravesically (600 μg/mL initial concentration) for 1 h/d for 2 consecutive days each month. The MMC concentration was escalated to a maximum of 800 μg/mL in groups of 3 dogs until the maximum tolerated dose (MTD) was determined. Serum assays for MMC were performed to determine the extent of systemic absorption of the MMC.


RESULTS
The MTD of MMC based on local toxicoses was 700 μg/mL (1-h dwell time, 2 consecutive days). In addition, 2 dogs had severe myelosuppression and appeared to have systemic absorption of MMC. Five dogs had partial remission, and 7 dogs had stable disease.


CONCLUSIONS
Intravesical MMC has antitumor activity in dogs with invasive TCC. Further study is needed to determine the cause of the myelosuppression associated with MMC administration, and to develop strategies to minimize this risk.
Abbo
A H
AH
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Jones
D R
DR
Masters
A R
AR
Stewart
J C
JC
Fourez
L
L
Knapp
D W
DW
D000283:Administration, Intravesical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000662:veterinary*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D020128:Inhibitory Concentration 50; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000662:veterinary*
D000970:Antineoplastic Agents; D016685:Mitomycin