Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer

More than 12,000 people are expected to die from invasive transitional cell carcinoma (TCC) of the urinary bladder each year in the United States, indicating that more effective therapy is needed. Drugs inhibiting cyclooxygenase (cox) have recently been found to have chemopreventive and antitumor ac...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2000, Vol.46 (3), p.221-226
Main Authors: KNAPP, D. W, GLICKMAN, N. W, WIDMER, W. R, DENICOLA, D. B, ADAMS, L. G, KUCZEK, T, BONNEY, P. L, DEGORTARI, A. E, HAN, C, GLICKMAN, L. T
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Carcinoma, Transitional Cell - drug therapy
Chemotherapy
Cisplatin - administration & dosage
Cisplatin - therapeutic use
Creatinine - blood
Cyclooxygenase Inhibitors - administration & dosage
Disease Models, Animal
Dogs
Female
Humans
Male
Medical sciences
Pharmacology. Drug treatments
Piroxicam - administration & dosage
Prospective Studies
Random Allocation
Urinary Bladder Neoplasms - drug therapy
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Summary:More than 12,000 people are expected to die from invasive transitional cell carcinoma (TCC) of the urinary bladder each year in the United States, indicating that more effective therapy is needed. Drugs inhibiting cyclooxygenase (cox) have recently been found to have chemopreventive and antitumor activity and may potentiate the effects of chemotherapy. The purpose of this study was to determine whether cisplatin combined with the cox-inhibitor piroxicam would induce remission more frequently than cisplatin alone in a relevant animal model of human invasive TCC. Pet dogs with naturally occurring, histopathologically confirmed, measurable TCC of the urinary bladder were randomized to receive cisplatin (60 mg/m2 i.v. every 21 days) or cisplatin (same dosage) combined with piroxicam (0.3 mg/kg orally every 24 h). Complete staging was performed prior to and at 6-week intervals during therapy. After eight dogs had been evaluated in each treatment group, a significant difference in remission rate was noted (Fisher's Exact test, P < 0.004). Tumor responses in the cisplatin/piroxicam group included two complete remissions (CR), four partial remissions (PR), two stable disease (SD), and no progressive disease (PD). Tumor responses to cisplatin alone in eight dogs were no CR, no PR, four SD, and four PD. Six additional dogs were treated with cisplatin/piroxicam, and in total 10 of 14 dogs had remission (two CR, eight PR). Renal toxicity of cisplatin/ piroxicam was frequent and dose limiting. Cisplatin/piroxicam induced remission more frequently than cisplatin alone in a canine model of human invasive TCC. Strategies to reduce renal toxicity need to be developed prior to evaluation of cisplatin/piroxicam in humans or general use of this treatment in pet dogs.
ISSN:0344-5704
1432-0843
DOI:10.1007/s002800000147