PHARMACODYNAMIC PHASE II BREAST, LUNG AND OVARY TRIALS

药效学 II 期乳腺、肺和卵巢试验

• 批准号: 2105012
• 负责人: JAMES H DOROSHOW
• 金额: $ 28.84万
• 依托单位: CITY OF HOPE NATIONAL MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-30 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2105012
• 关键词: anthracyclines; biopsy; breast neoplasms; clinical trials; combination cancer therapy; dosage; drug screening /evaluation; fluorouracil; folate; human subject; human therapy evaluation; immunocytochemistry; intermolecular interaction; leucovorin; lung neoplasms; multidrug resistance; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer pharmacology; nucleic acid sequence; ovary neoplasms; paclitaxel; pharmacokinetics; polymerase chain reaction

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.

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 乳房、肺和卵巢。这一目标将通过组建 分子药理学家和临床研究人员联盟 来自两个 NCI 指定的癌症中心和一家大型大学医院 将利用希望之城国家医院广泛的患者资源 医疗中心 (COH)、小肯尼斯·诺里斯综合癌症中心 南加州大学 (USC) 和 加州戴维斯癌症中心 (UCD) 将进行药理学指导 II 期临床试验重点关注：a) 新型高剂量化疗 通过回输外周血祖细胞，分子 叶酸-氟嘧啶相互作用的药效学，和 联合蒽环类药物耐药调节研究 晚期乳腺癌； b) 固有铂电阻的修改， 化疗剂量强化、新药开发和临床 对患有小细胞和非细胞疾病的个体进行辐射增敏 小细胞肺癌； c) 腹腔内靶向高剂量 患有卵巢癌的女性的化疗研究。这 应用程序正式化了一系列正在进行的协作交互 这三个机构自 20 世纪 80 年代中期以来就已存在。 基于每年超过 6,250 名新癌症患者 （其中乳腺癌710例，肺癌594例，肺癌157例） 1991 年的卵巢癌），以及该联盟在 骨髓移植领域、临床药效学 氟嘧啶类和抗叶醇类药物以及开创性经验 定量少量的相对基因表达 人体肿瘤组织、蒽环类药物的生化药理学和 铂类化合物及地区临床研究优势 化疗、新治疗方案的开发，以及 生物统计学和数据管理，COH-USC-UCD 第二阶段联盟 充分利用其临床研究专业知识来执行 对新药物和新药物进行复杂的、实验室支持的研究 提高癌症患者治疗效果的策略 乳房、肺和卵巢。