EFFECTS OF COMBINATION CHEMOTHERAPY INCLUDING CYCLOPHOSPHAMIDE, THP-ADRIAMYCIN, AND CISPLATIN ON THE DEVELOPMENT OF URINARY BLADDER CARCINOMA INDUCED BY N-BUTYL-N-(4-HYDROXYBUTYL) NITROSAMINE IN RATS

The present investigation was conducted to examine the effects of combination chemotherapy including Cyclophosphamide (CPM), THP-adriamycin (THP), and Cisplatin (CDDP) (CTP regimen) on the development of urinary bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats compared with CPM, adriamycin (ADM), and CDDP (CAP regimen). One hundred fiftyone male F344 rats were divided into 7 groups: Group 1 (BBN treatment alone), Group 2 (BBN treatment followed by CAP), Group 3 (BBN treatment followed by CTP), Group 4 (CAP without BBN treatment), Group 5 (CTP without BBN treatment), Group 6 (saline treatment alone), and Group 7 (untreated controls). All rats were sacrified 24 weeks after the beginning of the experiment. Bladder carcinoma was observed only in Groups 1 through 3. The incidence of carcinoma did not significantly differ between any two of these three groups, 29/30 (97%) for Group 1, 16/18 (89%) for Group 2, and 25/29 (86%) for Group 3. The grade and stage of the carcinoma were not suppressed by either treatment. The mean number of tumors was significantly lower in Group 3 than those in Group 1 (P<0.01) and in Group 2 (P<0.05). Renal changes were most marked and both CTP and CAP treatment groups showed proliferation of renal tubules and appearance of giant cells. No cardiotoxicity was observed in Group 5 although changes such as myocardiac fibrosis were observed in Group 4. These results suggest that THP is useful in the combination chemotherapy for invasive bladder cancer.