PHASE II TRIAL OF SOY PRIOR TO RADICAL PROSTATECTOMY

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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.