Interaction of antitumor agents including doxorubicin or daunorubicin in sarcoma-180 system

Abstract

Combination effect of antitumor agents, including doxorubicin and daunorubicin, was evaluated on the concept of pharmacological synergism in ascites sarcoma-180 system. In alternate adminsitration, combinations of doxorubicin plus cyclophosphamide, thio-TEPA, carboquone, actinomycin-D, vinblastine, vincristine, methotrexate, cytarabine, 6-mercaptopurine, or L-asparaginase showed synergism, but in simultaneous one, only three agents, cyclophosphamide, carboquone, and cytarabine, were synergistic. On the other hand, combination of daunorubicin plus one of 8 agents (thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, vinblastine, ancytabine, 6-mercaptopurine, and L-asparaginase) and 6 agents (cyclophosphamide, thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, and vinblastine) provided synergism in alternate and simultaneous administration. Combination effect of agents was affected by the schedule of drug administration for doxorubicin, but weak for daunorubicin. Toxicity of doxorubicin or daunorubicin in combination with other drugs was also affected by the schedule of administration. Combination of a larger number of agents in simultaneous administration provided antagonism compared with an alternate administration.