CHEMOPREVENTION OF OH-BBN-INDUCED BLADDER-CANCER IN MICE BY PIROXICAM

Piroxicam inhibited induction of transitional cell carcinoma in mouse urinary bladder by N-butyl-N-(4-hydroxybutyl)nitrosamine. At 15 mg pir oxicam/kg diet, tumor incidence was reduced 82% (P < 0.0001) compared with carcinogen controls. At 30 mg piroxicam/kg diet, tumor incidence was reduced 70% (P < 0.001). Results at the higher dose level suggeste d that piroxicam also may have inhibited invasion slightly. Combinatio n treatment with 2-difluoromethylornithine (DFMO) or all-trans-N-(4-hy droxyphenyl)retinamide (4-HPR) or both agents did not improve the chem opreventive potential of piroxicam. However, the three-agent combinati on of 30 mg piroxicam/kg, 1200 mg DFMO/kg and 313 mg 4-HPR/kg diet was highly effective. Tumor incidence was reduced 91% (P < 0.0001) compar ed with carcinogen controls. Unfortunately, the high efficacy was some what compromised by a significant decrease in survival and body weight gain in mice receiving the combination of agents compared with the ca rcinogen control.