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.

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