Titre du document / Document title

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

Auteur(s) / Author(s)

KNAPP D. W. ⁽¹⁾ ; GLICKMAN N. W. ⁽²⁾ ; WIDMER W. R. ⁽¹⁾ ; DENICOLA D. B. ⁽³⁾ ; ADAMS L. G. ⁽¹⁾ ; KUCZEK T. ⁽⁴⁾ ; BONNEY P. L. ⁽¹⁾ ; DEGORTARI A. E. ⁽¹⁾ ; HAN C. ⁽¹⁾ ; GLICKMAN L. T. ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907-1248, ETATS-UNIS
⁽²⁾ Research Programs, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, ETATS-UNIS
⁽³⁾ Department Veterinary Pathobiology, Purdue University, West Lafayette, IN 47907, ETATS-UNIS
⁽⁴⁾ Department of Statistics, Purdue University, West Lafayette, IN 47907, ETATS-UNIS

Résumé / Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Revue / Journal Title

Cancer chemotherapy and pharmacology   ISSN 0344-5704   CODEN CCPHDZ 

Source / Source

2000, vol. 46, n^o3, pp. 221-226 (27 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1978) (Revue)

Mots-clés anglais / English Keywords

Cisplatin ; Prostaglandin-endoperoxide synthase ; Piroxicam ; Animal ; Dog ; Animal model ; Malignant tumor ; Urinary bladder ; Invasion ; Human ; Transitional cell carcinoma ; Clinical trial ; Randomization ; Treatment ; Antineoplastic agent ; Chemotherapy ; Remission ; Toxicity ; Platinum II Complexes ; Oxicam derivatives ; Enzyme inhibitor ; Drug combination ; Treatment efficiency ; Oxidoreductases ; Enzyme ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Urinary system disease ; Urinary tract disease ; Bladder disease ;

Mots-clés français / French Keywords

Cisplatine ; Prostaglandin-endoperoxide synthase ; Piroxicam ; Animal ; Chien ; Modèle animal ; Tumeur maligne ; Vessie urinaire ; Invasion ; Homme ; Carcinome cellule transitionnelle ; Essai clinique ; Randomisation ; Traitement ; Anticancéreux ; Chimiothérapie ; Rémission ; Toxicité ; Platine II Complexe ; Oxicam dérivé ; Inhibiteur enzyme ; Association médicamenteuse ; Efficacité traitement ; Oxidoreductases ; Enzyme ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Appareil urinaire pathologie ; Voie urinaire pathologie ; Vessie pathologie ;

Mots-clés espagnols / Spanish Keywords

Cisplatino ; Prostaglandin-endoperoxide synthase ; Piroxicam ; Animal ; Perro ; Modelo animal ; Tumor maligno ; Vejiga ; Invasión ; Hombre ; Carcinoma célula transicional ; Ensayo clínico ; Aleatorización ; Tratamiento ; Anticanceroso ; Quimioterapia ; Remisión ; Toxicidad ; Platino II Complejo ; Oxicam derivado ; Inhibidor enzima ; Asociación medicamentosa ; Eficacia tratamiento ; Oxidoreductases ; Enzima ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Aparato urinario patología ; Vía urinaria patología ; Vejiga patología ;

Localisation / Location

INIST-CNRS, Cote INIST : 16820, 35400009193948.0070