INTRAPROSTATIC DOXORUBICIN THERAPY

前列腺内阿霉素治疗

• 批准号: 6223099
• 负责人: M GUILLAUME WIENTJES
• 金额: $ 3.7万
• 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/6223099
• 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：（申请人摘要）百分之六十的前列腺癌是 器官限制。 目前的局部治疗形式，即手术或 放射治疗会产生显着的长期副作用。 这 应用基于前列腺内化疗​​的假设 通过实现有效的药物代表了一种有前途的治疗选择 局部浓度，同时最大限度地减少全身暴露。 初步的 研究表明阿霉素浓度对人类有效 犬前列腺内注射后可实现前列腺肿瘤 注射时血浆浓度无毒。 该计划的目标 应用包括： 1) 建立阿霉素在以下领域中的有效 CxT： 人类前列腺肿瘤的体外培养，2) 研究前列腺内药物 狗和人类体内的分布和吸收动力学，3) 建立药代动力学和药效学的数学模型 基于血浆预测前列腺组织中药物 CxT 的参数 浓度以及前列腺 CxT 与治疗之间的关系 结果，4) 确定模型的有效性并生成 前列腺内注射疗效的初步临床信息 阿霉素用于前列腺癌患者。