PHASE I CLINICAL TRIALS OF ANTICANCER AGENTS

赠款的具体目标是： A.确定新抗癌药物对患者的急性毒性 癌症晚期。 B.重新定义现有药物的急性毒性和药代动力学 抗癌药物联合集落刺激给药 因素和其他毒性改良剂，可能有助于 探索更有效的剂量和时间表。 C.提供有关药理特性的信息 (吸收、分布、新陈代谢和消除) 抗肿瘤药物。 D.确定治疗方案，以评估抗肿瘤活性 第二阶段试验。 E.根据药理特点，建立适当的时相 特殊患者人群中的II剂量，如末梢功能受损的患者。 器官功能或严重预处理，老年人群，并 探索基于性别的药代动力学和药效学差异， 种族或民族群体。 F.获取有关药代动力学/药效学的初步信息 然后，与的相关性可以在第二阶段试验中扩展。 G.尽可能纳入辅助的基础实验室研究，并 适当的，以提高我们对生化和/或 药物作用的生物学机制。 拟研究的药物包括： A.NCIS药物筛选确定的细胞毒性化疗药物 程序。 B.具有新机制的细胞毒剂，包括抗血管生成 诱导剂、分化因子、凋亡诱导剂、反义 寡核苷酸和相关的基因特异性治疗药物，以及靶向 细胞毒剂。 C.现有的化疗药物，当与菌落一起给药时 改善剂量限制毒性的刺激因子或其他药物， 可给予的剂量比之前测试的剂量高得多。 D.由制药行业开发并提供给NCI的药物 用于协作开发。 这笔赠款应每年至少招收25-50名患者至至少3名 第一阶段试验每年进行一次，为期五年。药代动力学和/或 相关的实验室研究应成为这些研究的标准特征。 药代动力学将以持续的方式在接近 治疗，而不是以批处理的方式，以促进纳入 药代动力学数据在给药决策中的应用。一些第一阶段的研究 组合和/或调制研究可能不需要密集 药代动力学数据收集和这一点，以及将被 将在签订意向书(LOI)时确定 由项目人员进行评审或协议评审。

The specific goals of the grant 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 with 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. The agents to be studied will include the following: a. Cytotoxic chemotherapeutic agents identified by the NCIs drug screening program. b. Cytotoxic agents with novel mechanisms, including antiangiogenesis agents, differentiating agents, apoptosis-inducing agents, anti-sense oligonucleotides and related gene-specific therapeutic agents, and targeted cytoxic agents. C. Existing chemotherapeutic agents which, when administered with colony stimulating factors or other agents to ameliorate dose-limiting toxicities, can be given in doses substantially higher than those previously tested. d. Agents developed by the pharmaceutical industry and provided to the NCI for collaborative development. This grant shall accrue at least 25-50 patients per year to at least three active phase I trials per year for five years. Pharmacokinetics and/or correlative lab studies shall be a standard feature of these studies. Pharmacokinetics will be assessed in an ongoing manner in proximity to treatment rather than in a batched manner to facilitate incorporation of pharmacokinetic data in dosing decision-making. Some phase I studies of combination and/or modulation studies may not require intensive pharmacokinetic data collection and this, as well as the credit to be assigned, will be determined at the time of the Letter of intent (LOI) review or protocol review by program staff.