Iigo M, Kanzawa F, Nakamura A, Hoshi A, Kuretani K
Gan. 1977 Aug;68(4):459-64.
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.
在腹水肉瘤-180系统中,基于药理协同作用的概念评估了包括阿霉素和柔红霉素在内的抗肿瘤药物的联合效应。在交替给药时,阿霉素与环磷酰胺、噻替派、卡波醌、放线菌素-D、长春碱、长春新碱、甲氨蝶呤、阿糖胞苷、6-巯基嘌呤或L-天冬酰胺酶的联合显示出协同作用,但在同时给药时,只有三种药物,即环磷酰胺、卡波醌和阿糖胞苷具有协同作用。另一方面,柔红霉素与8种药物(噻替派、丝裂霉素-C、博来霉素、放线菌素-D、长春碱、安西他滨、6-巯基嘌呤和L-天冬酰胺酶)中的一种以及6种药物(环磷酰胺、噻替派、丝裂霉素-C、博来霉素、放线菌素-D和长春碱)的联合在交替和同时给药时均产生协同作用。药物的联合效应受阿霉素给药方案的影响,但受柔红霉素的影响较弱。阿霉素或柔红霉素与其他药物联合使用时的毒性也受给药方案的影响。与交替给药相比,同时给药时联合使用更多药物会产生拮抗作用。