PHASE II TRIAL OF SOY PRIOR TO RADICAL PROSTATECTOMY

描述（由申请人提供）：本项目的目的是在患有临床局限性前列腺癌的男性中进行一项两组（n = 30/组）随机、双盲、安慰剂对照的II期临床试验，在根治性前列腺切除术前4-6周给予大豆分离蛋白。安慰剂将是一种基于酪蛋白的制剂;除了蛋白质来源和大豆特异性化合物（如异黄酮，包括染料木素）外，两种制剂的组成相同。这些制剂目前用于根治性乳房切除术后的男性试验，没有任何副作用。剂量为20 g蛋白质/天，提供约24-26/天的染料木黄酮和约40-43/天的总黄酮。比较治疗组和安慰剂组，将在根治性直肠癌切除术标本中检查以下相关中间终点。主要终点将是最大癌症病灶中增殖细胞（MIB-1）标记指数和凋亡细胞（TUNEL）标记指数的组间差异。次要终点是微血管密度（血管生成）、血清和前列腺组织中大豆异黄酮（特别是染料木素）的浓度。我们还将确定干预（大豆分离蛋白）是否调节化合物特异性参数，特别是酪氨酸激酶的活性，作为酪氨酸磷酸化的程度，预计将被大豆衍生的染料木黄酮抑制。这些参数的相关变化将表明生物活性大豆成分已到达预期的靶组织。另一个次要终点是血清胆固醇，预计大豆异黄酮可降低血清胆固醇。其他探索性终点包括基线和干预结束时的血清PSA水平、病理肿瘤特征（级别和阶段），癌症程度和高级别PIN，核因子的单一复合测量HGPIN和癌症中的细胞核大小、形状和质地以及倍性，前列腺特异性抗原（PSA）、前列腺特异性膜抗原（PSMA）、Her-2/neu和UROC 28的组织表达，一种新的前列腺癌相关标志物，将被研究。这项研究将产生有关大豆异黄酮对前列腺的生物利用度以及通过短期大豆蛋白干预调节前列腺和血清中相关中间点的信息。

DESCRIPTION (provided by applicant): The objective of this project is to conduct a two arm (n = 30/arm) randomized, double-blind, placebo controlled phase II clinical trial in men with clinically localized prostate cancer with administration of soy protein isolate in the 4-6 weeks prior to radical prostatectomy. The placebo will be a casein-based preparation; both preparations are identical in composition except for the source of protein and soy-specific compounds such as isoflavones including genistein. These preparations are currently used in trials with men after radical prostatectomy without any side effects. The dose will be 20 g protein/day providing approximately 24-26/day genistein and approximately 40-43/day total isoflavones). Comparing the treatment and placebo groups, the following relevant intermediate end-points will be examined in the radical prostatectomy specimens. Primary endpoints will be differences between groups in the proliferating cell (MIB-1) labeling index and the apoptotic cell (TUNEL) labeling index in the largest focus of cancer. Secondary end-points are microvessel density (angiogenesis), the serum and prostate tissue concentrations of soy isoflavones (specifically genistein). We will also determine whether the intervention (soy protein isolate) modulates a compound-specific parameter, specifically the activity of tyrosine kinase, as the extent of tyrosine phosphorylaton, which is expected to be inhibited by the soy-derived genistein. Relevant changes in these parameters would indicate that biologically active soy constituents have reached the intended target tissue. An additional secondary endpoint is serum cholesterol that is expected to decreased by soy isoflavones. Additional exploratory endpoints include serum PSA levels at baseline and at the end of intervention, pathological tumor characteristics (grade and stage), extent of cancer and high grade PIN, a single compound measure of nuclear factors (nuclear size, shape, and texture) and ploidy in HGPIN and cancer, tissue expression of prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), Her-2/neu, and UROC28, a novel prostate cancer-associated marker, will be studied. This study will yield information about bioavaUability of soy isoflavones to the prostate and about modulation of relevant intermediate en-points in the prostate and serum by short-term soy protein intervention.