Use of spontaneously arising canine TCC as a relevant model of late-stage human bladder cancer in which to assess the novel drug, Tavocept™, for its ability to mitigate toxicity and improve efficacy of a cisplatin and piroxicam combination therapy protocol
Carolyn J. Henry
900 East Campus Drive; UMC; Columbia, MO, 65211, USA
Abstract:
Transitional cell carcinoma (TCC) of the urinary bladder occurs naturally in dogs and is usually of advanced stage at the time of diagnosis, such that standard successful human therapies are ineffective. As such, canine TCC is analogous to human muscle-invasive bladder cancer and can serve as an excellent translational model for assessment of novel treatment options for late-stage disease. A combination of cisplatin and piroxicam has provided the best response rates (>71%) for canine TCC; however, drug-induced nephrotoxicity is a frequent and dose-limiting complication precluding clinical use of this protocol. The investigational drug Tavocept™ (BioNumerik Pharmaceuticals; San Antonio, TX, USA) targets the thioredoxin and glutaredoxin systems and prevents or mitigates cisplatin-induced renal toxicity in normal dogs and rats, as well as human cancer patients. Tavocept™ has also been shown to enhance antitumor activity of cisplatin in animal and human studies. We have conducted preclinical studies assessing the cytotoxic effects of Tavocept™, cisplatin, piroxicam, and combinations thereof on three canine TCC cell lines. Cytotoxicity of cisplatin was potentiated by Tavocept™ in all three cell lines, providing further impetus to proceed with a canine clinical trial. We are currently conducting a prospective trial of this combination therapy in dogs with naturally-occurring TCC.
