Abstract:
The inhibitory effects of the combination of 1,2:5,6-dianhydrogalactitol (DAG) and maytansine (MAY) on the growth of Ehrlich ascites cancer (EAC), L1210 leukemia, ascites hepatoma, B 16 melanoma, sarcoma 180 and bone marrow stem ceils in mice were studied. Simultaneous administration or sequential administration of the two drugs with a time interval of 24 hours, independent of their order, produced a synergistic inhibitory effect on EAC, showing a prolongation of the life span of the mice or reduction of the number of tumor cells. The result obtained with L1210 leukemia was similar to that obtained with EAC, except for simultaneous administration of the two drugs. When DAG Was given 24 hours before MAY, the inhibition of tumor weight in B 16 melanoma on day 21 was found to be more than the additive effect of either drug, but the survival time of the tumor-bearing mice was not prolonged. In experiments with both ascites hepatoma and sarcoma 180, no synergism of the combination chemotherapy was observed. The combination of DAG and MAY produced less cell kill than the additive effect of the two drugs on normal bone marrow stem cells. From our data it would seem advantageous to administer these two agents, separated by a time interval of 24 hours, rather than giving them simultaneously.