Pretreatment tumor prostaglandin E2 concentration and cyclooxygenase-2 expression are not associated with the response of canine naturally occurring invasive urinary bladder cancer to cyclooxygenase inhibitor therapy.

The purpose of this study was to determine the extent to which pretreatment prostaglandin E2 (PGE2) concentration and cyclooxygenase-2 (cox-2) expression could be used to predict the antitumor activity of cox inhibitor treatment in naturally occurring canine transitional cell carcinoma of the urinary bladder (TCC). Snap frozen tissues (to measure PGE2) and formalin-fixed TCC samples (for cox-2 immunohistochemistry) were obtained by cystoscopy or surgery. Complete tumor staging was performed before and after one month of treatment with the cox inhibitor, piroxicam (0.3 mg/kg q24 h po). The pretreatment PGE2 concentration ranged from 57 to 1624 ng/g of TCC tissue; n=18 dogs). Cox-2 immunoreactivity was observed in all TCC samples. There was no association between PGE2 concentration, cox-2 expression, and change in tumor volume with piroxicam treatment. In conclusion, cox-2 expression or PGE2 concentration alone, or the combination of the two was not useful in predicting response to piroxicam treatment in canine TCC.

Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder.

Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox) inhibitor has shown promise against canine TCC, where the disease closely mimics the human condition. A phase II clinical trial of carboplatin combined with the cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring, histopathologically confirmed, measurable TCC. Complete tumour staging was performed before and at 6-week intervals during therapy. Tumour responses in 29 dogs included 11 partial remissions, 13 stable disease and five progressive disease. Two of the 31 dogs were withdrawn prior to the re-staging of the tumour. Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted in 11 dogs. The median survival was 161 days from first carboplatin treatment to death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs providing evidence that a cox inhibitor enhances the antitumour activity of carboplatin. The frequent toxicity and limited survival, however, do not support the use of this specific protocol against TCC.

Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs.

OBJECTIVE: To evaluate the use of piroxicam for the treatment of oral squamous cell carcinoma in dogs. DESIGN: Prospective case series. ANIMALS: 17 dogs with measurable oral squamous cell carcinoma. PROCEDURE: Dogs were treated with piroxicam at a dosage of 0.3 mg/kg (0.14 mg/lb) of body weight, PO, every 24 hours until progressive disease or unacceptable signs of toxicosis developed or the dog died. RESULTS: One dog had a complete remission (maxillary tumor), and 2 dogs had partial remissions (lingual tumor and tonsillar tumor). An additional 5 dogs had stable disease, including 1 with a maxillary tumor, 2 with mandibular tumors, and 2 with tonsillar tumors. Variables associated with tumor response were not identified. Median and mean times to failure for the 3 dogs that had a remission were 180 and 223 days, respectively. Median and mean times to failure for the 5 dogs with stable disease were 102 and 223 days, respectively. Time to failure was positively associated with tumor response and negatively associated with tumor size. One dog had mild adverse gastrointestinal tract effects that resolved with the addition of misoprostol to the treatment regimen. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that piroxicam may be useful in the treatment of dogs with oral squamous cell carcinoma; response rate was similar to that reported for other cytotoxic treatments. Larger-scale studies are warranted to determine what role piroxicam may have, alone or in combination with other treatments, for the treatment of dogs with oral squamous cell carcinoma.