INTRAPROSTATIC DOXORUBICIN THERAPY

前列腺内阿霉素治疗

• 批准号: 2895941
• 负责人: M GUILLAUME WIENTJES
• 金额: $ 31.45万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-19 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2895941
• 关键词: clinical research; dogs; doxorubicin; human subject; human therapy evaluation; injection /infusion; male; mathematical model; model design /development; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; outcomes research; pharmacokinetics; prostate neoplasms; tissue /cell culture

DESCRIPTION: (Applicant's Abstract) Sixty percent of prostate cancers are organ-confined. Current local forms of therapy, namely surgery or radiotherapy, produce significant long-lasting side effects. This application is based on the hypothesis that intraprostatic chemotherapy represents a promising treatment option by achieving effective drug concentrations locally while minimizing systemic exposure. Preliminary studies demonstrate that doxorubicin concentrations effective against human prostate tumors can be achieved in the dog prostate after intraprostatic injection while plasma concentrations are non-toxic. The objectives of the application are: 1) to establish the effective CxT of doxorubicin using in vitro cultures of human prostate tumors, 2) to study the intraprostatic drug distribution and absorption kinetics in vivo in dogs and humans, 3) to develop a mathematical model of pharmacokinetic and pharmacodynamic parameters to predict the drug CxT in prostate tissue based on the plasma concentration and the relationship between prostate CxT and treatment outcome, and 4) to determine the validity of the model and to generate preliminary clinical information on the efficacy of intraprostatic doxorubicin in patients with prostate cancer.

描述：（申请人的摘要）60％的前列腺癌为 器官限制。 当前的局部治疗形式，即手术或 放射疗法会产生明显的长期副作用。 这 应用是基于肉眼化疗的假设 通过获得有效的药物来代表有前途的治疗选择 局部浓度，同时最大程度地减少全身暴露。 初步的 研究表明，阿霉素浓度有效 肉体内后，可以在狗前列腺中实现前列腺肿瘤 注射时血浆浓度无毒。 目标的目标 应用是：1）使用In建立阿霉素的有效CXT 人类前列腺肿瘤的体外培养物，2）研究肉体内药物 在狗和人类体内分布和吸收动力学，3） 开发药代动力学和药效学的数学模型 基于等离子体预测前列腺组织中的药物CXT的参数 集中度以及前列腺CXT与治疗之间的关系 结果，以及4）确定模型的有效性并生成 有关肉体内疗效的初步临床信息 前列腺癌患者的阿霉素。