CHEMICAL MODIFIERS OF RADIATION AND CHEMOTHERAPY

在斯坦福大学，有一个正在进行的项目，涉及化学改性剂， 放疗和化疗 这些药物虽然没有 抗肿瘤活性本身能够通过以下方式增强肿瘤细胞杀伤： 放疗或化疗，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 合作组临床试验，最终将提供车辆 来测试这些药剂 此应用程序正在请求支持 用于开发性临床试验，这是 从基础科学实验室到一般临床使用的药物， 为必要的接口科学，以最佳方式连接诊所和 实验室 开发性临床试验（I期和II期试验） 包括给药、药代动力学分析、毒性评估 药物相关毒性的治疗，如果可能的话，改变药物 给药以减轻或预防毒性。 近距离临床和 斯坦福大学的实验室互动极大地促进了我们的能力， 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机制，并设计新药或 修改现有的药物以减少毒性，从而提高药物疗效 和实用性。 有四个密切相关的领域需要研究：放射增敏剂， 化学增敏剂，增加细胞内巯基含量作为一种手段， 正常组织保护和细胞内巯基耗竭作为一种手段， 增加肿瘤对辐射、药物和缺氧细胞的敏感性 放射增敏剂。 这些调查利用了这样一个事实， 当肿瘤和正常组织都被 接受放疗或化疗。 通过致敏肿瘤和 保护剂量限制的正常组织，治疗指数将是 增加，这可能导致局部控制率的改善， 某些肿瘤的可治愈性。 此外，还计划进行研究， 化学改性剂与粒子放射治疗计划相结合 在加州伯克利大学。

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.