PHASE I TRIALS OF ANTICANCER AGENTS

抗癌药物的 I 期试验

• 批准号: 6448472
• 负责人: JUDITH KARP
• 金额: $ 39.12万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-15 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6448472
• 关键词: acute leukemia; angiogenesis inhibitors; antineoplastics; apoptosis; butyrates; carboplatin; cell differentiation; clinical research; clinical trial phase I; colony stimulating factor; combination cancer therapy; cytotoxicity; drug administration rate /duration; drug metabolism; drug screening /evaluation; flow cytometry; gender difference; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; pharmacokinetics; prodrugs; racial /ethnic difference; retinoids

The premise behind this grant application if that characterization and understanding of the pharmacology of an antineoplastic agent should allow better utilization of that agent in the clinical arena. Impeccable characterization of the clinical toxicities and maximum tolerated dose of an agent is no longer sufficient. Pharmacologic characteristics of an agent that ideally would be developed in its initial clinical trials include: pharmacokinetics, metabolism and pharmacodynamic manifestations on molecular and cellular, as well as, clinical levels. With this abiding philosophy and hypothesis, it is our intent to provide scientifically directed Phase I trials of promising anti-cancer agents available through the National Cancer Institute. The agents may come from the NCI's drug screening program, or may be referred to the NCI from outside sources. In pursuit of this specific aim, we intend to apply principles well established at our institution regarding integration of drug metabolism, pharmacokinetics, and pharmacokinetic/pharmacodynamic relationships into clinical trial designs. Furthermore, we intend to extend our activities integrating information regarding the mechanism of action into clinical trial design, and interpretation of the pharmaco-dynamic consequences of drug therapy. The specific goals of the application are: a) To define the acute toxicities of new anticancer agents in patients with advanced cancer; b) to re-define the acute toxicities and pharmacokinetics of existing anticancer agents administered in combination with colony stimulating factors and other toxicity-ameliorating agents, which may facilitate the exploration of more effective doses and schedules; c) to provide information on the pharmacologic characteristics (absorption, distribution, metabolism, and elimination) of selected antitumor agents; d) to define treatment regimens for evaluation of antitumor activity in Phase II trials; e) based on pharmacologic characteristics, to establish appropriate Phase II doses in special patient populations, such as those with impaired end-organ function or with heavy pretreatment, geriatric populations, and to explore pharmacokinetic and pharmacodynamic differences based on gender, race or ethnic group; f) to obtain preliminary information on pharmacokinetic/pharmacodynamic, correlations which can then be extended in Phase II trials; g) to incorporate ancillary basic laboratory studies, when possible and appropriate, to enhance our understanding of the biochemical and/or biological mechanisms of drug actions.

如果该特征和 了解抗塑料剂的药理学应 在临床领域，可以更好地利用该药物。 临床毒性和最大的无可挑剔的表征 代理的耐受剂量不再足够。 药理学 理想情况下将在其中发展的代理的特征 最初的临床试验包括：药代动力学，代谢和 分子和细胞的药效学表现，以及 临床水平。 有了这种持久的哲学和假设，这是我们的 意图提供科学定向的I阶段试验 通过国家癌症研究所获得的抗癌代理。 这 代理商可能来自NCI的药物筛查计划，或者可能是 从外部来源提到NCI。 追求这一特定 目的，我们打算应用在我们机构中建立的良好的原则 关于药物代谢，药代动力学和 药代动力学/药效学与临床试验 设计。 此外，我们打算扩展我们的活动 有关临床试验中作用机制的信息 药物的药物动态后果的设计和解释 治疗。 应用程序的具体目标是：a）定义 晚期患者的新抗癌药的急性毒性 癌症; b）重新定义急性毒性和药代动力学 现有的抗癌剂与菌落结合 刺激因素和其他毒性明确的剂，这可能 促进探索更有效的剂量和时间表； c）到 提供有关药理学特征的信息（吸收， 选定抗肿瘤剂的分布，代谢和消除； d）定义治疗方案以评估抗肿瘤活性 II期试验； e）基于药理特征，以建立 特殊患者人群中的适当第二阶段剂量，例如 最终器官功能受损或高度预处理，老年病 种群，并探索药代动力学和药效学 基于性别，种族或种族群体的差异； f）获得 有关药代动力学/药效，相关性的初步信息 然后可以在II期试验中扩展； g）合并 辅助基础实验室研究，尽可能适当地 增强我们对生化和/或生物学的理解 毒品作用的机制。