Effects of interferon in combination with cytotoxic drugs on mouse bladder tumor (MBT-2) growth in vitro and in vivo

The effects of interferon alone and in combination with either adriamycin, mitomycin C or thiotepa were evaluated for antiproliferative activity for the mouse bladder tumor, MBT-2. In vitro dose response studies with adriamycin, mitomycin C and thiotepa showed dose dependent antiproliferative activity over a concentration range of .001 microgram./ml. to 10 microgram./ml. Interferon also exhibited dose dependent inhibition over a dose range of 250 units/ml. to 4000 units/ml. Comparative in vitro antiproliferative studies showed adriamycin to consistently be the most inhibitory cytotoxic drug followed by mitomycin C and thiotepa. Interferon and thiotepa produce similar (35%) inhibition at the highest concentrations studied. In vitro studies assessing the effects of interferon (1000 units/ml.) combined with each cytotoxic drug (0.01 to 1.0 microgram./ml.) were performed. The most effective combination was observed to be interferon and adriamycin. In three of four experiments either additivity or synergism was observed while consistently augmented activity was not observed with interferon combined with either thiotepa or mitomycin C. In vivo studies on MBT-2 tumors implanted intravesically showed no antitumor activity for adriamycin alone, interferon alone or a combination of both. These results show that combination intravesical therapy with interferon and adriamycin is not an effective treatment regimen in the mouse model when administered as described in this report. These data further suggest that combinations of interferon and cytotoxic drugs may not provide improved response rates in patients treated for superficial bladder tumors.