Effectiveness of long-term chemotherapy and/or BCG on murine bladder cancer

Abstract

Cure following surgery of bladder cancer is limited by recurrence of the original tumor or by the development of new primary tumors. TCC of the bladder induced in C3H/HeJ mice by FANFT closely resemble their human counterpart and have been used to evaluate the effect of chemotherapy and/or BCG on the induction and growth of these tumors. Three hundred five mice were divided into a control group of 30 and 11 treatment groups of 25. Therapy was initiated at 5 and 7 months after FANFT. The first tumors in this system are observed at 8 months with an expected incidence of 70-90% by 11 months. Therapy consisted of: 1) BCG; 2) cyclophosphamide; 3) cyclophosphamide + BCG; 4) cyclophosphamide + 5-FU; 5) cyclophosphamide + adriamycin; and 6) adriamycin. All mice were killed after 11 months on FANFT. Bladders were wieghed and the tumors were staged. Tumor incidence was reduced by only two regimens: adriamycin and cyclophosphamide + adriamycin. Cyclophosphamide significantly reduced subsequent tumor volume compared with the control group, with the effect being more pronounced in mice beginning treatment at 5 months. The combination regimens were superior to cyclophosphamide alone. BCG did not potentiate the antitumor action of cyclophosphamide and, when used alone, actually enhanced tumor growth (P less than 0.025). The use of BCG immunotherapy should be cautioned, but the effectiveness of the antineoplastic drugs suggests their use in clinical trials in patients with bladder cancer.