EVALUATION OF COMBINATION THERAPY FOR ANTICANCER ACTIVIT

合同的总体目标是在临床前确定 设定，治疗上协同的抗肿瘤药物组合，可以 将在临床试验中进一步评估。为了实现这一目标 目的：单药和任何一种药物的临床前抗肿瘤活性 细胞毒性抗肿瘤药物、生物反应调节剂或 将对生化调节剂进行比较以确定是否有 联合使用比单独使用组成 组合。大多数实验将在体内进行， 但有时在体外进行初步试验会更合适。 进行评价，以便深入了解 药物的组合和/或排序的重要性。活体内 选择用于研究的模型将取决于将要使用的化合物 已评估。在适当的情况下，模型将利用小鼠肿瘤或 人肿瘤移植瘤生长在无病原体、有免疫能力或有免疫能力的环境中 缺陷小鼠(例如，无症状、SCID)小鼠。曾经是添加剂或增效剂 已确定组合，可进行更多研究以 在第二个模型中确认效果和/或优化治疗 通过修改剂量比例、时间表、顺序进行响应 和/或定时。

The overall objective of the contract is to identify, in a preclinical setting, therapeutically synergistic antitumor drug combinations that can be further evaluated in clinical trials. In order to accomplish this objective, the preclinical antitumor activity of single agents and any combination of cytotoxic antitumor agents, biological response modifiers or a biochemical modulator will be compared to determine whether any combination is more efficacious than the individual agents comprising the combination. The majority of the experiments will be conducted in vivo, but on occasion it will be more appropriate to conduct preliminary in vitro evaluations in order to gain insight into the potential synergy of the combination and/or the importance of sequencing of the agents. The in vivo models selected for the studies will be dependent upon the compounds to be evaluated. As appropriate, the models will utilize either murine tumors or human tumor xenografts growing in pathogen-free immune-competent or immune- deficient (e.g., athymic, SCID) mice. Once an additive or synergistic combination has been identified, additional studies may be conducted to confirm the effect in a second model and/or to optimize the therapeutic response through modification of either dosage ratio, schedule, sequencing and/or timing.