EFFECT OF DRUG COMBINATION ON ANTITUMOR ACTIVITY AND MYELOTOXICITY

  • 1 January 1976
    • journal article
    • research article
    • Vol. 67  (2) , 207-214
Abstract
Relationship between the survival time of L-1210 leukemia bearing mice and myelosuppression of normal mice after combination chemotherapy was studied. In a variety of combinations of 6-mercaptopurine, 6-thioguanine and cyclophosphamide, a combination of cyclophosphamide and 6-thiolguanine produced the highest increase in life span (ILS) and the highest number of 60 day survivors. A combination of 6-mercaptopurine and 6-thioguanine showed as low an ILS as single agents. A combination of 6-mercaptopurine, cyclophosphamide and 6-thioguanine exhibited the 2nd best effect on survival time of leukemic mice. In myelosuppression, as measured by changes in the total number of nucleated cells, in the number of hematopoietic colony-forming cells and in peroxidase level of femoral bone marrow, the combination of 6-mercaptopurine and 6-thiolguanine showed no more toxicity than the other 2 drug combinations. In addition to these findings, the presence of a striking difference in cell number in ascitic fluid of leukemic mice among the animals given 6-mercaptopurine and 6-thiolguanine, and those given other 2- or 3 drug combinations may suggest that the difference in antileukemic activity is not due to the difference in toxicity against the host, but due to the difference in the activity of direct action of combined drugs on leukemic cells in the peritoneal cavity or other sites.