toremifene followed by radical prostatectomy in treating patients with stage i or stage ii prostate cancer

Conditions: Prostate Cancer

Summary: rationale: androgens can stimulate the growth of prostate cancer cells. hormone therapy using toremifene may fight prostate cancer by reducing the production of androgens. purpose: randomized phase ii trial to study the effectiveness of toremifene followed by radical prostatectomy in treating patients who have stage i or stage ii prostate cancer.

objectives: * compare the percent of high-grade prostatic intraepithelial neoplasia (hgpin) present in the radical prostatectomy tissue (excluding the luminal area) of patients with stage i or ii adenocarcinoma of the prostate treated with toremifene vs observation alone followed by radical prostatectomy. * compare the absolute and relative changes in hgpin in patients treated with toremifene vs observation alone. * compare biomarkers (including dna ploidy and nuclear morphology; ki67 and mib-1 expression; bcl-2 expression; frequency of cells expressing apoptotic bodies; microvessel density; and intraprostatic testosterone, dihydrotestosterone (dht), and estradiol) in the radical prostatectomy tissue of patients treated with toremifene vs observation alone. * compare changes from baseline in serum biomarkers, particularly psa and hormone profiles (testosterone, dht, androstenedione, dehydroepiandrosterone, androstanediol-glucuronide, estradiol, and sex hormone binding globulin), in patients treated with toremifene vs observation alone. * compare the safety of toremifene in these patients. * determine the relationships among pairs of biomarkers, biomarker changes, and outcome measures, including toxicity of toremifene and posttreatment hgpin in these patients. * determine the relationship between hgpin or biomarker responses and antiandrogen germline cag repeat length polymorphism in patients treated with toremifene. * compare the tumor volume, margin status, and pt stage in patients treated with toremifene vs observation alone. outline: this is a randomized, open-label, multicenter study. patients are stratified according to participating center and baseline high-grade prostatic intraepithelial neoplasia (none vs more than 0% up to 10% vs more than 10%). patients are randomized to 1 of 2 treatment arms. * arm i: patients receive oral toremifene daily for 3-6 weeks in the absence of unacceptable toxicity. * arm ii: patients undergo observation alone. patients in both arms then undergo radical prostatectomy. projected accrual: a total of 78 patients (52 for arm i, 26 for arm ii) will be accrued for this study at a rate of 6-7 patients per month.

Eligibility criteria:
disease characteristics: * histologically confirmed adenocarcinoma of the prostate * organ-confined (ct1-2) disease (stage i or ii) * must be schedule to undergo radical prostatectomy * prior sextant biopsy required patient characteristics: age: * over 18 performance status: * ecog 0-1 life expectancy: * not specified hematopoietic: * neutrophil count greater than 1,500/mm\^3 * platelet count greater than 100,000/mm\^3 hepatic: * bilirubin less than 1.5 times upper limit of normal (uln) * alt and ast less than 2 times uln * alkaline phosphatase less than 2 times uln * no chronic hepatitis or cirrhosis renal: * creatinine less than 1.5 times uln other: * no severe mental or physical illness that would preclude radical prostatectomy * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * not specified chemotherapy: * not specified endocrine therapy: * at least 5 years since prior antiestrogen, antiandrogen, lhrh agonist, estrogen, or progestational agent radiotherapy: * not specified surgery: * see disease characteristics

Keywords: adenocarcinoma of the prostate stage i prostate cancer stage ii prostate cancer