Nishikawa K, Kusama K, Ekimoto H, Takahashi K
Gan To Kagaku Ryoho. 1989 Dec;16(12):3739-45.
Combination effects of etoposide (ET) with each of 10 antitumor drugs were examined with P 388 leukemia cells in vitro and in vivo. Median effect analysis was applied for the evaluation of in vitro effect by the growth inhibition, and the in vivo effect by comparison of the increase of life span (ILS) in a combined group with the sum of ILS's in 2 single agent groups. Among 10 drugs combined with ET, cyclophosphamide (melphalan was used for in vitro study), cisplatin and 6-mercaptopurine exhibited a strong synergism both in vitro and in vivo. The combination of ET with mitomycin C, vincristine, vindesine or cytarabine produced additive or slightly synergistic effect in the both systems. However, methotrexate + ET combination showed an antagonistic effect. Although the combination of ET with doxorubicin or fluorouracil showed a slight synergism in vitro, it was antagonistic in vivo. Thus, the in vitro and in vivo combined effects were consistent in 8 of 10 drugs. The employed methods in the present studies could distinguish high efficacy of ET + cyclophosphamide and ET + cisplatin, which are clinically approved as effective combinations against lung cancer. The methods seem to be useful to assess the drug efficacy in experimental combination.
在体外和体内用P 388白血病细胞检测了依托泊苷（ET）与10种抗肿瘤药物各自的联合效应。采用中位效应分析来评估体外生长抑制效应，以及通过比较联合组的寿命延长（ILS）与两个单药组ILS之和来评估体内效应。在与ET联合使用的10种药物中，环磷酰胺（体外研究使用美法仑）、顺铂和6-巯基嘌呤在体外和体内均表现出强烈的协同作用。ET与丝裂霉素C、长春新碱、长春地辛或阿糖胞苷的联合在两个系统中产生相加或轻微的协同作用。然而，甲氨蝶呤+ET联合显示出拮抗作用。虽然ET与阿霉素或氟尿嘧啶的联合在体外显示出轻微的协同作用，但在体内却是拮抗作用。因此，10种药物中有8种药物的体外和体内联合效应是一致的。本研究中采用的方法能够区分ET +环磷酰胺和ET +顺铂的高效性，这两种联合用药在临床上被批准为治疗肺癌的有效组合。这些方法似乎有助于评估实验性联合用药中的药物疗效。
