CHEMOPREVENTION TRIAL OF DIFLUOROMETHYLORNITHINE IN FAMILIAL PROSTATE CANCER

二氟甲基鸟氨酸治疗家族性前列腺癌的化学预防试验

• 批准号: 6260559
• 负责人: THOMAS AHLERING
• 金额: $ 24.38万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6260559
• 关键词: cancer prevention; cancer risk; carcinogenesis inhibitor; chemoprevention; clinical research; cooperative study; difluoromethylornithine; drug screening /evaluation; family genetics; human subject; human therapy evaluation; male; polyamines; prostate neoplasms

The long-term objective of this Project is to reduce the morbidity and mortality from prostate cancer by preventing its development, promotion, or progression by interrupting polyamine synthesis. The major hypothesis to be tested is to determine whether alpha-difluoromethylornithine (DFMO), an enzyme activated irreversible inhibitor of ornithine decarboxylase (the rate-limiting step of polyamine syntheses), can suppress tissue polyamine content and progression-related genes in prostate tissue of individuals at high genetic risk for prostate cancer. Two major specific aims will be addressed: (1) to conduct a randomized, placebo-controlled, double-blind phase IIB trial of DFMO in bothers and fir-cousin males of probands with familial history of early onset prostate cancer (identified by Project I). (2) to carefully assess the side effects of DFMO in this population and to compare them to the biological effects on the prostate gland. Surrogate endpoint biomarkers (Project II) will be measured in the prostate gland obtained by sextant biopsy at baseline and post-treatment (after one year). Baseline and post-treatment free and total PSA density will also be measured. Appropriate correlations with modulation of surrogate endpoint biomarkers will be assessed. The long-term goal of the Project is to determine if suppression of prostate polyamine contents is an effective strategy for prevention of prostate cancer in human males.

该项目的长期目标是通过中断多胺合成来预防前列腺癌的发生、促进或进展，从而降低前列腺癌的发病率和死亡率。要测试的主要假设是确定α-二氟甲基鸟氨酸（DFMO），一种酶激活的鸟氨酸脱羧酶（多胺合成的限速步骤）的不可逆抑制剂，是否可以抑制前列腺组织中的组织多胺含量和进展相关基因。前列腺癌遗传风险高的个体。将解决两个主要的具体目标：（1）在具有早发性前列腺癌家族史（由项目 I 确定）的先证者的亲属和远亲男性中进行 DFMO 的随机、安慰剂对照、双盲 IIB 期试验。 ）。 (2) 仔细评估 DFMO 在该人群中的副作用，并将其与对前列腺的生物学效应进行比较。将在基线和治疗后（一年后）通过六分仪活检获得的前列腺中测量替代终点生物标志物（项目 II）。还将测量基线和未治疗后的 PSA 密度和总 PSA 密度。将评估与替代终点生物标志物调节的适当相关性。该项目的长期目标是确定抑制前列腺多胺含量是否是预防人类男性前列腺癌的有效策略。