Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC.
Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary leaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E2 (PGE2) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified. Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 month intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable disiroxicam (Feldene) is a nonsteroidal anti-inflammatory P drug primarily used to treat arthritis in humans.' It has also been reported to have antitumor activity in chemically inducal2-' and transplanted* tumors in rodents and in metastatic tumors in people.' We previously reported a phase I clinical trial of piroxicam in 62 dogs with naturally occurring tumors and identified dose-related gastrointestinal toxicity and subclinical renal toxicity.'o Antitumor activity was observed in this phase 1 trial in dogs with transitional cell carcinoma (TCC) of the urinary bladder." To hrther investigate the antitumor activity of piroxicam, we conducted a phase I1 clinical trial in 25 dogs with TCC of the bladder. The study reported here includes 9 dogs from the phase I trial and 25 dogs from the phase I1 trial. Although the purpose of a phase I trial is to evaluate drug doses and toxicity, useful information on tumor response and survival was available in the dogs with TCC in the phase I trial we conducted." Therefore, these dogs were included in this report. Materials and Methods Clinical Trial DesignEntry requirements for this study included the presence of measurable (by cystography), histopathologically confirmed TCC of the urinary bladder, performance status consistent with expected minimum survival of6 weeks, and informed consent by the owner. Dogs that had previously received chemotherapy had evidence of tumor progression on that therapy, and a minimum of 3 weeks was required between the last chemotherapy and entry into this trial.Dogs were evaluated at the Purdue University Veterinary Teaching Hospital on days 0, 28, and 56. These evaluations included physical examination, complete blood count, serum biochemistry profile, urinalysis, thoracic radiography, and cystography (pneumocystography or double contrast cystography). Care was taken to perform the cystography in the same manner (same radiographic technique, same amount of contrast material) for each evaluation of a patient. Piroxicam was administered orally at a dose of 0.3 mg/kg sid. This dose was established based on a previous phase I clinical trial." When secondary bacteria...
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