diindolylmethane in treating patients with nonmetastatic prostate cancer that has not responded to previous hormone therapy

Conditions: Prostate Cancer

Summary: rationale: diindolylmethane may slow the growth of prostate cancer cells. purpose: this phase i trial is studying the side effects and best dose of diindolylmethane in treating patients with nonmetastatic prostate cancer that has not responded to previous hormone therapy.

objectives: primary * establish the maximum tolerated dose, dose-limiting toxicity, and a recommended phase ii dose of absorption-enhanced diindolylmethane (bioresponse-dim\^® \[br-dim\]) in patients with nonmetastatic, hormone-refractory prostate cancer and rising serum prostate-specific antigen (psa) levels. * evaluate the toxicities of br-dim. secondary * evaluate the plasma pharmacokinetics of twice daily oral administration of br-dim in this patient population. * evaluate the effect of br-dim supplementation on serum psa level. * correlate changes in expression levels of lymphocytes nf-kb with serum psa levels in patients taking br-dim supplementation. * determine quality of life measures in patients taking br-dim supplementation. outline: this is an open-label, dose-escalation study. patients receive oral absorption-enhanced absorption-enhanced diindolylmethane (bioresponse-dim\^® \[br-dim\]) twice daily on days 1-28. treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of br-dim until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. at least 6 patients are treated at the mtd. quality of life is assessed at baseline, on day 1 of each course, and at the completion of study therapy. projected accrual: a total of 36 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically proven adenocarcinoma of the prostate * prostate specific antigen (psa)-only failure after local therapy (surgery, radiation therapy, brachytherapy, or cryotherapy) * rising psa despite androgen-deprivation therapy with castrate levels of testosterone (\< 50 ng/dl) * two successive rising psa levels at least 1 week apart * psa ≥ 5 ng/ml * patients with a history of combined hormonal therapy must continue luteinizing-hormone releasing-hormone agonist treatment but must demonstrate rising psa after anti-androgen withdrawal * no evidence of distant metastasis by bone scan and ct scan * no known brain metastases requiring active therapy patient characteristics: * ecog performance status ≤ 3 * life expectancy ≥ 12 weeks * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * hemoglobin ≥ 8.0 g/dl * total bilirubin ≤ 1.5 times upper limit of normal (uln) * sgot and/or sgpt ≤ 2.5 times uln and alkaline phosphatase normal or alkaline phosphatase ≤ 4 times uln and sgot and/or sgpt normal * creatinine clearance ≥ 60 ml/min or creatinine normal * fertile patients must use effective contraception * none of the following conditions within the past 6 months: * myocardial infarction * severe or unstable angina * symptomatic congestive heart failure * cerebrovascular accident or transient ischemic attack * coronary/peripheral artery bypass grafting * no other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation prior concurrent therapy: * see disease characteristics * at least 28 days since prior radiotherapy * at least 28 days since prior investigational agents for treatment of prostate cancer * at least 4 weeks since prior flutamide * at least 6 weeks since prior bicalutamide * no other concurrent antineoplastic agents * no concurrent warfarin-related anticoagulants * no concurrent proton-pump inhibitor drugs for gastroesophageal reflux disease (e.g., rabeprazole, esomeprazole magnesium, lansoprazole, omeprazole, or pantoprazole sodium) * no concurrent micronutrient supplements or dietary soy products * one daily multivitamin allowed

Keywords: recurrent prostate cancer stage i prostate cancer stage ii prostate cancer stage iii prostate cancer adenocarcinoma of the prostate stage iv prostate cancer