00896-A: Phase I Clinical Trial and Pharmacokinetics of Intravesical Mytomycin C (MMC) for the Treatment of Canine Transitional Cell Carcinoma (TC) of the Urinary Bladder
Grant Status: Closed
AbstractApproximately 30,000 pet dogs develop urinary bladder cancer (transitional cell carcinoma or ""TCC"") yearly in the United States, and its prevalence is increasing. Breeds that have the highest risk for the development of this lethal cancer include the Scottish Terrier, West Highland White Terrier, Shetland Sheepdog, Wirehair Fox Terrier, and Beagle. The major cause of death in pet dogs with invasive TCC is urinary obstruction, i.e. most dogs with TCC die from ""local disease"" (the cancer within the bladder itself). Intravenous chemotherapy is given in an attempt to reduce tumor size, delay tumor growth, and prevent urinary obstruction. But, intravenous chemotherapy is only partially effective, and it causes side effects in many dogs. We propse to study a different, potentially much more effective approach to deliver chemotherapy, this directly into the urinary bladder through a urinary catheter. The advantage to this form of therapy is that high concentrations of chemotherapy (which kills more cancer cells) come in direct contact with the cancer. At the same time, side effects to other organs are minimized because less (or none) of the chemotherapy reaches normal organs in the body. We propose to study a chemotherapeutic drug called mitomycin C (MMC) given by intravesical route to dogs. MMC had not yet been formally studied in dogs with TCC, but it has been given to laboratory dogs (without cancer) with no side effects being noted. We have administered intravesical MMC to 7 dogs with TCC as a salvage treatment after they had failed to respond to other therapies. Two dogs have had partial remission (less than or equal to 50 percent reduction in tumor volume). One of the dogs who had remission, had cancer which had become resistant to at least 6 other anticancer drugs. In addition to the 2 dogs with remission, the other 5 dogs treated with MMC have had stable disease, i.e. the MMC treatment stopped the TCC from growing. Here we propse a clinical trial to determine the antitumor activity, safety, and most appropriate dosage of MMC in pet dogs with naturally-occuring invasive TCC. The successful results of this study will provide a new beneficial treatment option for pet dogs with TCC.
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