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：（申请人的摘要）60%的前列腺癌是 器官受限 目前的局部治疗形式，即手术或 放疗，产生显著的长期副作用。 这 应用是基于前列腺内化疗 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 研究表明，阿霉素浓度有效地对抗人类， 前列腺内注射后， 注射，而血浆浓度是无毒的。 的目标 应用是：1）建立有效的CxT的阿霉素用于 体外培养人前列腺肿瘤，2）研究前列腺内药物 犬和人体内分布和吸收动力学，3） 建立药代动力学和药效学的数学模型 参数，以预测药物CxT在前列腺组织的基础上，血浆 浓度以及前列腺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 前列腺内注射有效性的初步临床信息 阿霉素治疗前列腺癌