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Cox-2 Inhibitors in Transition Cell Carcinoma

Note for Pet Owners:  

This information is provided by Provet for educational purposes only.

You should seek the advice of your veterinarian if your pet is ill as only he or she can correctly advise on the diagnosis and recommend the treatment that is most appropriate for your pet.

Work conducted in the USA suggests Cox-2 inhibitors may be useful in the management of Transition Cell Carcinoma of the urinary bladder in dogs and humans

The histopathological appearance, biological behaviour and response to treatment of naturally-occurring transitional cell carcinoma (TCC) of the urinary bladder is very similar in humans and dogs. In dogs surgical excision is usually difficult because the tumour is often located in the trigome region of the bladder and once metastasis is present survival times are not good, being less than one year in humans and less than 110 days in dogs. Studies in the USA supported by the Morris Animal Foundation and the National Institutes of Health have been looking at the use of cyclooxygenase (cox) inhibitors as antitumour agents in transition cell carcinoma. Cox-2 is expressed in most canine and human transition cell carcinoma cases and in clinical trials piroxicam (a cox-1 and cox-2 inhibitor) has been given to 62 dogs with TCC. 

Tumour responses to therapy have included: 

  • 2 complete remission
  • 9 partial remission (>50% reduction in tumour volume)
  • 35 stable disease (<50% change in tumour volume), and 
  • 16 progressive disease (>50% increase in tumour volume or new tumour lesions). 

These results are reportedly as good as or better than those for chemotherapy. 

As a result of the positive results from these canine studies, 2 clinical trials of cox inhibitors in people with urinary bladder cancer have been initiated at Indiana University (Dr. R. Foster, PI). In one trial, patients with high grade carcinoma which has not yet invaded and which has not responded to conventional therapy are being treated with piroxicam. Two of the initial 5 patients in this study have had complete remission of their cancer. In a second clinical trial, patients with invasive TCC are being treated with a cox-2 inhibitor between diagnosis and cystectomy. In 3 of the 5 patients in this study apoptosis has been noted. 

In conclusion, the use of Cox-2  inhibitor therapy in TCC looks very promising in both dogs and humans.

Reference

D. Knapp, S. I. Mohammed, R. S. Foster, L. Cheng and W. R. Widmer. Clinical Trials in Urinary Bladder Cancer - Translation from Dogs to Humans In : Genes, Dogs and Cancer 3rd Annual Cancer Conference - 2003, Modiano J.F (Ed). International Veterinary Information Service, Ithaca NY (www.ivis.org), 2003; P3002.0903

Subsequently the effect of NSAIDs has been shown not to be due to a cytotoxic effect :

Knapp DW , Kazak T , Park B
Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 
American Journal of Veterinary Research 1995, 56(6):801-805

Abstract

Piroxicam and other nonsteroidal anti-inflammatory drugs (NSAID) have antitumor activity against naturally acquired cancer in dogs and human beings, and against experimentally induced tumors in rodents. We are investigating potential mechanisms of NSAID antitumor activity. The direct cytotoxicity of piroxicam indomethacin, and aspirin against 4 canine tumor cell lines (transitional cell carcinoma, squamous cell carcinoma, melanoma, and soft tissue sarcoma) was determined in short-term growth rate assays and in clonogenic assays. Piroxicam was evaluated alone and in combination with the lipoxygenase inhibitor zileuton, and in combination with the chemotherapeutic agents cisplatin and carboplatin. The 50% inhibitory concentrations (IC50) against melanoma cells in short-term growth rate assays were: 530 microM piroxicam, 180 microM indomethacin, and greater than 1 mM aspirin. These IC50 values were over 10 times greater than serum concentrations of these drugs that could safely be achieved in vivo. The IC50 of zileuton combined with piroxicam (280 microM) was not different from the IC50 of zileuton alone (230 microM; ANOVA P = 0.47) in melanoma cells. Similarly, addition of piroxicam did not alter the IC50 of either cisplatin (1.6 microM) or carboplatin (6.1 microM). These results suggest that NSAID, at serum concentrations achievable in vivo, do not have direct cytotoxicity against canine tumor cells tested. It is unlikely that the in vivo antitumor activity of NSAID is attributable to a direct cytotoxic effect.

 

Updated January 2016 

 
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