Durand R E, Goldie J H
Cancer Treat Rep. 1987 Jul-Aug;71(7-8):673-9.
Some clinical data suggest that etoposide and cisplatin may be synergistic against certain types of tumors. Since studies of the process are both easier and more precise in laboratory systems, we have used V79 spheroids as a model to quantify the interaction of the drugs in cycling and noncycling, aerobic, and hypoxic cell subpopulations. The degree of interaction between etoposide and cisplatin in this system, quantified using the median-effect analysis, was highly dependent on the overall treatment toxicity, and to a lesser extent, the subpopulation of cells assessed. Synergism was demonstrated for relatively modest (1 decade) cell kills achievable at clinically relevant drug doses; increasing the toxicity of the combination treatment by increasing the cisplatin level produced a greater relative gain in the noncycling and hypoxic cells than in the aerobic, cycling cells of the spheroids.
一些临床数据表明，依托泊苷和顺铂对某些类型的肿瘤可能具有协同作用。由于在实验室系统中对这一过程的研究既更容易也更精确，我们使用V79球体作为模型，来量化药物在循环和非循环、需氧和缺氧细胞亚群中的相互作用。在该系统中，依托泊苷和顺铂之间的相互作用程度通过中位效应分析进行量化，高度依赖于总体治疗毒性，在较小程度上也依赖于所评估的细胞亚群。对于在临床相关药物剂量下可实现的相对适度（1个对数级）的细胞杀伤，证明存在协同作用；通过提高顺铂水平增加联合治疗的毒性，在非循环和缺氧细胞中产生的相对增益比在球体的需氧、循环细胞中更大。
