COOPERATIVE STUDY

本申请是代表芝加哥大学提交的， 一个由伊利诺斯州三家附属社区医院组成的财团， 印第安纳州。该提案的目的是研究新的II期药物， 标准疗法难治的实体瘤的治疗 包括乳腺癌，非小细胞肺癌，前列腺癌， 结直肠癌、头颈癌和肾癌。这些研究 寻求在这些疾病中确定新药剂的活性。此外，本发明还提供了一种方法， 我们建议研究的群体药代动力学和药效学 抗癌单一药剂和/或组合，并确定它们的 治疗结果的重要性，包括毒性和反应。我们 将寻求开发优化治疗的药理学模型， 抗癌剂的比例，并协助个体化给药。的 拟议的研究将在芝加哥大学进行， 附属医院。这些机构此前曾合作 并在开展多机构临床研究方面有着良好的记录， research.预计将有多达40名患者的四项II期试验 每一项都将每年在该联合会内进行。在 此外，还有一个坚实的制度基础， 基于新的抗癌药物的临床研究。样本协议 用于吡嗪重氮氢氧化物或苏拉明的II期试验， 乳腺癌、结肠直肠癌、前列腺癌、非小细胞肺癌和肾癌， 分别关于伴随治疗的附加样本方案 提供了头颈癌的化学放射疗法。在这些 研究新的单一药物或组合的临床活性， 将研究最低程度预治疗的患者人群。此外，本发明还提供了一种方法， 将建立详细的动力学和药效学曲线。

This application is submitted on behalf of the University of Chicago and a consortium of three affiliated community hospitals in Illinois and Indiana. The aims of this proposal are to study new phase II agents in the treatment of solid tumors that are refractory to standard therapy including breast cancer, non-small cell lung cancer, prostate cancer, colorectal cancer head and neck cancer and renal cancer. These studies seek to establish activity of new agents in these diseases. In addition, we propose to study population pharmacokinetics and pharmacodynamics of anticancer single agents and/or combinations, and to determine their significance for treatment outcome including toxicity and response. We will seek to develop pharmacologic models that optimize the therapeutic ratio of anticancer agents and assist in individualized dosing. The proposed studies will be conducted at the University of Chicago and three affiliated hospitals. These institutions have previously worked together and have a firm track record of conducting multiinstitutional clinical research. It is expected that four phase Il trials of up to 40 patients each will be conducted on an annual basis within this consortium. In addition there is a solid institutional foundation of pharmacologically based clinical investigations of new anticancer agents. Sample protocols are provided for phase II trials of pyrazine diazo hydroxide or suramin in breast, colorectal, prostate, non-small cell lung and renal cancer, respectively. An additional sample protocol on concomitant chemoradiotherapy in head and neck cancer is provided. In each of these studies clinical activity of a new single agent or combination in a minimally pretreated patient population will be investigated. In addition, a detailed kinetic and pharmacodynamic profile will be established.