Phase I Study of Bioresponse-dim in Non-Metastatic, Hormone-Refractory Prostate Cancer Patients With Rising Serum PSA
Phase I Study of Bioresponse-dim in Non-Metastatic, Hormone-Refractory Prostate Cancer Patients With Rising Serum PSA
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
Secondary
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)
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:
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