CHEMICAL MODIFIERS OF RADIATION AND CHEMOTHERAPY

在斯坦福大学，有一项正在进行的计划，涉及化学修饰剂 放疗和化疗。这些都是毒品，虽然没有 抗肿瘤活性本身能够通过以下方式增强对肿瘤细胞的杀伤 放射或化疗，或保护正常组织。我们有一个 广泛的药物开发计划和坚定的合作承诺 最终将提供载体的合作小组临床试验 对这些代理商进行测试。此应用程序正在请求支持 对于开发临床试验，这是需要的主要步骤 从基础科学实验室到一般临床使用的药物，以及 对于以最佳方式连接临床和医疗中心所需的接口科学 实验室。发展性临床试验(I期和II期试验) 包括药物给药、药代动力学分析、毒性评估 与药物有关的毒性的治疗，以及如有可能，更换药物 给药以减轻或防止毒性。密切的临床和 斯坦福大学的实验室互动极大地促进了我们 设计最佳临床试验，评估其结果，研究 在实验室中研究药物毒性的机制，并设计新药或 修改现有的药物以降低毒性，从而提高药物疗效 和实用性。 有四个密切相关的领域需要调查：放射增敏剂， 化学增敏剂，增加细胞内硫醇含量作为一种手段 正常的组织保护和细胞内硫醇耗竭作为一种手段 增加肿瘤对辐射、药物和低氧细胞的敏感性 放射增敏剂。这些调查利用了这样一个事实，即 当肿瘤和正常组织都存在剂量-反应关系 用放射或化疗治疗的。通过致敏肿瘤和 保护剂量有限的正常组织的治疗指数将是 增加，这可能导致当地控制率的改善和 某些肿瘤的可治性。此外，还计划对其进行研究 化学改良剂与粒子放射治疗计划相结合 在加州大学伯克利分校。

At Stanford there is an ongoing program involving chemical modifiers of radiation and chemotherapy. These are drugs, which, while not having antitumor activity per se, are able to either enhance tumor cell killing by radiation or chemotherapy, or to protect normal tissues. We have an extensive drug development program and a strong commitment to collaborative cooperative group clinical trials which will ultimately provide the vehicle for the testing of these agents. This application is requesting support for the developmental clinical trials, which is the major step required for a drug to go from the basic science laboratory to general clinical use, and for the interfacing science necessary to optimally link the clinic and the laboratory. The developmental clinical trials (Phase I and II trials) include drug administration, pharmacokinetic analysis, toxicity assessment, treatment of drug related toxicity, and, if possible, alteration of drug administration to lessen or prevent toxicity. The close clinical and laboratory interaction at Stanford greatly facilitates our ability to design an optimal clinical trial, to assess its results, to study mechanisms of drug toxicity in the laboratory, and to design new drugs or modify existing ones to reduce toxicity, thereby increasing drug efficacy and utility. There are four closely related areas to be investigated: radiosensitizers, chemosensitizers, augmentation of intracellular thiol content as a means of normal tissue protection, and intracellular thiol depletion as a means of increasing tumor sensitivity to irradiation, to drugs, and to hypoxic cell radiosensitizers. These investigations exploit the fact that a dose-response relationship exists when both tumors and normal tissues are treated with radiation or chemotherapy. By sensitizing tumors and protecting dose-limiting normal tissues the therapeutic index will be increased which could lead to an improvement in the local control rate and curability of certain tumors. In addition studies are planned for the use of chemical modifiers in conjunction with the particle radiotherapy program at University of California Berkeley.