PHARMACODYNAMIC PHASE II BREAST, LUNG AND OVARY TRIALS

该提案的目标是开发新颖的、基于实验室的 癌症患者的化疗治疗策略 乳腺肺和卵巢这一目标将通过组建 一个由分子药理学家和临床研究者组成的联盟 来自两个NCI指定的癌症中心和一个大型大学医院， 将利用国家希望之城的广泛患者资源， 医学中心（COH），小肯尼斯诺里斯。综合癌症中心 在南加州大学（USC）和 加州戴维斯癌症中心（UCD）进行药理学指导 II期临床试验，重点是：a）新型高剂量化疗 与外周血祖细胞回输，分子 叶酸-氟嘧啶相互作用的药效学，以及 蒽环类药物联合耐药调节研究 晚期乳腺癌; B）固有铂抗性的改变， 化疗剂量强化、新药开发和临床 小细胞和非小细胞肺癌患者的辐射敏感性 小细胞肺癌;和c）靶向腹膜内和高剂量 卵巢癌的治疗方法有哪些？这 应用程序将一系列正在进行的协作交互正式化 在这三个机构中，从八十年代中期就存在了。 根据每年超过6，250名新癌症患者的可用性 （包括710名乳腺癌患者，594名肺癌患者和157名 卵巢癌1991年），并在财团的主要优势， 骨髓移植领域， 氟嘧啶和抗氟素，以及开创性的经验 在定量相对基因表达从少量的 人肿瘤组织，蒽环类抗生素的生化药理学， 铂化合物，以及区域临床研究优势 化疗，开发新的治疗方案，以及 生物统计学和数据管理，COH-USC-UCD第二阶段联盟是 充分利用其临床研究专长， 复杂的，实验室支持的研究，新的代理和新的 提高癌症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.