CHEMICAL MODIFIERS OF RADIATION AND CHEMOTHERAPY

这项申请是为了继续支持临床和 实验室计划，开发和优化化学品的使用 放射或化疗的改良剂。修饰语，而 本身并不一定具有治疗价值，会改变 肿瘤或正常组织对治疗的反应导致 卓越的肿瘤控制和减少正常组织损伤。在… 联合放射治疗中心，我们已经组建了一个 一组调查人员，他们可以从 基本概念，通过药物开发和最初的 第一阶段和第二阶段试验，到大规模的疗效试验。这群人 包括具有不同专业领域的基础科学家，以及 来自癌症护理各个方面的临床医生。主要强调的是 临床试验将是对 低氧细胞放射增敏剂，特别是药物SR 2508。 最近的数据表明，肿瘤既有急性的，也有 慢性低氧细胞，低氧细胞很可能是 具有临床意义，而且电子亲和敏化剂 有治疗效果。因此，解决问题的方法 低氧细胞用SR 2508低氧细胞毒剂和 全氟碳化物是有保证的。SR递送的新方法 2508，通过持续输注和瘤内注射 将对药物相关的胶原基质进行评估。我们会 研究肿瘤的氧合和生化状态 在体内分割放射治疗过程中，以优化 各种化学改良剂在临床上的应用。我们有 建立了研究SR神经病变的体外系统 2508在试图改善其剂量限制毒性时， 从而进一步提高了该药剂的实用性。基于 梅法兰的随机II期试验的阳性结果- 我们将继续使用咪唑类药物 硝基咪唑类化合物作为化学增粘剂。硫醇修饰可以 提高低氧细胞放射增敏剂的疗效，并改变 肿瘤与正常组织的化疗敏感性和放射敏感性 纸巾。我们将进行实验室研究和临床试验，如果 被认为是适当的，具有以下两种情况之一的代理 谷胱甘肽和其他硫醇。相互关联的临床与临床 本申请中提出的实验室研究提供了一种 也是联合中心其他项目的重要基础 为国家临床试验提供指导和支持 感光剂。

This application is for the continued support of the clinical and laboratory program to develop, and optimize the use of chemical modifiers of radiation or chemotherapy. The modifiers, while not necessary of therapeutic value by themselves, will alter the response of tumors or normal tissues to treatment resulting in superior tumor control and reduction in normal tissue injury. At the Joint Center for Radiation Therapy we have assembled a group of investigators who can develop these approaches from the basic concept, through drug development and the initial Phase I and II trials, to large scale efficacy trials. This group includes basic scientists with different areas of expertise, and clinicans from all aspects of cancer care. The major emphasis of the clinical trials will be the continuation of the use of the hypoxic cell radiosensitizers, particularly the drug SR 2508. Recent data suggest that tumors have both acutely and chronically hypoxic cells, that hypoxic cells may well be clinically significant, and that the electron affinic sensitizers have therapeutic efficacy. Therefore, the approach to the hypoxic cell with SR 2508 hypoxic cell cytoxic agents and perfluorocarbons is warranted. Novel methods of delivery of SR 2508, by continuous infusion and by intratumoral injection with a drug-associated collagen matrix will be evaluated. We will investigate the oxygenation and biochemical status of tumors during fractionated radiotherapy in vivo in order to optimize the utility of the various chemical modifiers in the clinic. We have established an in vitro system to study the neuropathy of SR 2508 in an attempt to ameliorate its the dose-limiting toxicity, thereby further increasing the utility of this agent. Based on the positive results of a randomized phase II trail of mephalan - Misonidazole we will continue to pursue the use of nitroimidazoles as chemosenitizers. Thiol modifications can increase the efficacy of hypoxic cell radiosensitizers, and alter chemosensitivity and radiosensitivy of tumors and normal tissues. We will conduct laboratory studies, and clinical trials, if deemed appropriate, with agents that either or augment glutathione and other thiols. The interrelated clinical and laboratory research proposed in this application, provides an important base for other programs of the Joint Center, as well as providing direction and support for national clinical trials with sensitizers.