INTRAPROSTATIC DOXORUBICIN THERAPY

描述：(申请者摘要)60%的前列腺癌 器官受限。目前的局部治疗形式，即手术或 放射治疗，会产生显著的长期副作用。这 应用是基于这样一种假设，即前列腺内化疗 通过获得有效的药物，代表了一种有希望的治疗选择 在局部集中，同时最大限度地减少全身暴露。初步 研究表明阿霉素浓度对人类有效 经前列腺腔内注射后可在犬前列腺内形成前列腺癌 在血浆浓度无毒的情况下注射。该计划的目标 应用：1)建立阿霉素类药物的有效CXT 人前列腺癌的体外培养，2)前列腺腔内药物研究 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 基于血药浓度预测药物CXT在前列腺组织中的参数 前列腺癌CXT的浓度及其与治疗的关系 结果，以及4)确定模型的有效性并生成 前列腺腔内注射疗效的初步临床资料 阿霉素在前列腺癌患者中的应用。

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.