PHASE II TRIAL OF SOY PRIOR TO RADICAL PROSTATECTOMY

描述（由申请人提供）：该项目的目的是在根治性前列腺切除术前4-6周给予大豆分离蛋白的临床局限性前列腺癌男性患者进行一项两组（n = 30/组）随机、双盲、安慰剂对照的II期临床试验。安慰剂将是一种基于酪蛋白的制剂；除了蛋白质和大豆特异性化合物如异黄酮（包括染料木素）的来源不同，这两种制剂在组成上是相同的。这些制剂目前用于根治性前列腺切除术后的男性试验，没有任何副作用。剂量为20克蛋白质/天，提供约24-26个/天染料木素和约40-43个/天总异黄酮)。比较治疗组和安慰剂组，将在根治性前列腺切除术标本中检查以下相关的中间终点。主要终点将是肿瘤最大焦点增殖细胞（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，酪氨酸磷酸化预计会被大豆来源的染料木素抑制。这些参数的相关变化表明具有生物活性的大豆成分已经到达预定的目标组织。另一个次要终点是血清胆固醇，预计大豆异黄酮会降低血清胆固醇。其他探索终点包括基线和干预结束时的血清PSA水平、病理肿瘤特征（分级和分期）、癌症程度和高分级PIN、核因素（核大小、形状和质地）的单一复合测量以及HGPIN和癌症的倍性、前列腺特异性抗原（PSA）、前列腺特异性膜抗原（PSMA）、Her-2/neu和新型前列腺癌相关标志物UROC28的组织表达。本研究将提供大豆异黄酮对前列腺的生物利用度以及短期大豆蛋白干预对前列腺和血清中相关中间点的调节信息。

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.