Prophylaxis and Therapy of an Experimental Bladder Cancer with Biological Response Modifiers

Abstract

We have previously reported that the intraperitoneal injection of viable bacillus Calmette-Guerin (BCG) reduces the incidence of tumor takes and the rate of tumor growth and also increases tumor regression rate and survival in C3H/HeN mice challenged with the syngeneic MBT-2 bladder cancer. We have now investigated the immunoprophylactic effect of BCG and other biological response modifiers. Groups of 12 to 15 female C3H/HeN mice were challenged with 5 X 10(5) MBT-2 viable cells and treated with BCG, poly I:C, tilorone, levamisole or a combination of these agents. Appropriate controls were included in each experiment. In this study we confirmed previous findings that BCG alone is effective in prophylaxis and can also decrease the rate of tumor growth in those animals not protected against tumor takes. Both i.p. levamisole and oral tilorone lacked activity against the MBT-2 tumor. A single i.p. injection of poly I:C was also ineffective although its repeated administration reduced the rate of tumor growth and induced a significant number of tumor regressions. Combined therapy of BCG with either levamisole or tilorone offered no therapeutic advantage over BCG alone. Heat-inactivated BCG also failed to induce anti-tumor activity in C3H/HeN mice challenged with MBT-2 cells. These results indicate that live BCG remains the most active immunoprophylactic and immunotherapeutic agent against the MBT-2 murine bladder cancer. Furthermore, the anti-tumor effect of viable BCG is not potentiated further by the addition of other immune modulating agents.

Biological Response Modifiers for the Treatment of Superficial Bladder Tumors

“…This compound has also been investigated in the eighties for superficial bladder cancer therapy. Both Reichert and Lamm [11]and Morales and Pang [12]observed that BCG was superior to levamisole in inhibiting MBT-2 bladder tumor growth in mice. In 10 patients who had undergone repeated surgical resections for recurrent superficial bladder cancer treated with levamisole, Romics et al [13]found that 4 patients only remained free from recurrence over 1 year.…”