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...