PHARMACODYNAMIC PHASE II BREAST, LUNG AND OVARY TRIALS

这项提议的目标是开发以实验室为基础的新型 肺癌患者的化疗策略 乳房、肺和卵巢。这一目标将通过编队来实现 由分子药理学家和临床研究人员组成的联盟 来自NCI指定的两个癌症中心和一家大型大学医院 将利用国家希望之城丰富的病人资源 医疗中心(COH)，The Kenneth Norris，Jr.综合性癌症中心 在南加州大学(USC)和加州大学 加州戴维斯癌症中心(UCD)将在药物指导下进行 第二阶段临床试验的重点是：a)新的大剂量化疗 随着外周血祖细胞的回输，分子 叶酸-氟嘧啶相互作用的药效学，以及 联合应用蒽环类药物耐药调节研究治疗慢性粒细胞白血病 晚期乳腺癌；b)修改固有的铂耐药， 化疗剂量强化、新药开发和临床 小细胞和非小细胞疾病患者的放射增敏 小细胞肺癌；以及c)靶向腹膜内和大剂量 卵巢癌患者的化疗研究。这 应用程序使一系列持续的协作交互正式化 在这三个机构中，自20世纪80年代中期以来一直存在的S。 基于每年有超过6250名新的癌症患者 (其中乳腺癌710例，肺癌594例，肺癌157例 1991年卵巢癌)，以及该财团在 骨髓移植的领域、临床药效学 氟嘧啶类药物和抗癌药物，以及开创性经验 在对相对基因表达的定量研究中 人体肿瘤组织、蒽环类药物的生化药理作用 铂类化合物和地区临床研究实力 化疗，开发新的治疗方案，以及 生物统计和数据管理，COH-USC-UCD第二阶段联盟是 处于有利地位，利用其临床研究专业知识进行 对新制剂和新制剂进行复杂的实验室支持的研究 提高肺癌患者治疗效果的策略 乳房、肺和卵巢。

The objective of this proposal is to develop novel, laboratory-based chemotherapeutic treatment strategies for patients with cancers of the breast, lung, and ovary. This goal will be pursued through the formation of a consortium of molecular pharmacologists and clinical investigators from two NCI-designated Cancer Centers and a large University Hospital who will utilize the extensive patient resources of the City of Hope National Medical Center (COH), the Kenneth Norris, Jr. Comprehensive Cancer Center at the University of Southern California (USC), and the University of California, Davis Cancer Center (UCD) to perform pharmacologically-guided Phase II clinical trials that focus on: a) novel high-dose chemotherapies with peripheral blood progenitor cell reinfusion, the molecular pharmacodynamics of the folate-fluoropyrimidine interaction, and combination anthracycline resistance modulation studies for patients with advanced breast cancer; b) modification of intrinsic platinum resistance, chemotherapy dose intensification, new agent development, and clinical radiation sensitization for individuals suffering from small cell and non- small cell lung cancer; and c) targeted intraperitoneal and high-dose chemotherapy investigations for women with cancer of the ovary. This application formalizes an ongoing series of collaborative interactions among these three institutions that have existed since the mid-1980's. Based on the availability of over 6,250 new cancer patients per year (including 710 with breast cancer, 594 with lung cancer, and 157 with ovarian cancer in 1991), and on the major strengths of the consortium in the areas of bone marrow transplantation, the clinical pharmacodynamics of the fluoropyrimidines and the antifols, as well as pioneering experience in the quantitation of relative gene expression from small amounts of human tumor tissue, the biochemical pharmacology of the anthracyclines and platinum compounds, and clinical research strengths in regional chemotherapy, the development of novel treatment regimens, and biostatistics and data management, the COH-USC-UCD Phase II Consortium is well-positioned to utilize its clinical research expertise to perform complex, laboratory-supported investigations of both new agents and new strategies to enhance therapeutic outcomes for patients with cancers of the breast, lung, and ovary.