The effect of platinum analogues and combination chemotherapy on murine bladder cancer

Cis-diamminedichloroplatinum II currently is the most effective chemotherapeutic agent in advanced bladder cancer. However, most of the objective responses are partial and/or of limited duration (average 6 months). In an effort to identify a more effective compound with less toxicity platinum analogues have been synthesized. Since results in the carcinogen-induced murine bladder cancer model have correlated with activity of drugs in man this model was used to evaluate 4 of these analogues. Although not as effective as the parent compound, cis-diamminedichloroplatinum, they exhibited significant antitumor activity in the poorly differentiated transplanted tumor. However, they were not able to reduce the incidence or size of primary tumors. Another approach to enhance tumor cell kill is combination chemotherapy. The addition of cyclophosphamide or cyclophosphamide and doxorubicin hydrochloride to cis-diamminedichloroplatinum produced a greater tumor inhibition than cis-diamminedichloroplatinum alone in experiments with the transplanted and the primary tumor models. It is hoped that these studies will continue to provide background information for the design of disease oriented phase I and II clinical trials.