COMBINATION THERAPY FOR ANTICANCER ACTIVITY

合同的总体目标是在临床前 背景、治疗协同抗肿瘤药物组合， 在临床试验中进一步评估。 要实现这一 目的，临床前抗肿瘤活性的单一药物和任何 细胞毒性抗肿瘤剂、生物反应调节剂或 将比较生物化学调节剂以确定是否存在任何 组合物比包含组合物的单独药剂更有效。 组合. 大多数实验将在体内进行， 但有时更适合在体外进行初步研究 评价，以便深入了解联合国系统 组合和/或试剂测序的重要性。 体内 为研究选择的模型将取决于要 评估。 适当时，模型将利用鼠肿瘤或 人肿瘤异种移植物在无病原体的免疫活性或免疫活性的 有缺陷的（例如，无胸腺，SCID）小鼠。 一旦添加或协同 如果已经确定了联合用药，可能会进行额外的研究， 在第二模型中确认效果和/或优化治疗 通过调整剂量比、时间表、顺序 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.