RATIONALE: Drugs used in chemotherapy, such as eflornithine, work in different ways to stop
tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of
prostate cancer cells. Drugs used in hormone therapy, such as bicalutamide, may fight
prostate cancer by stopping the adrenal glands from producing androgens. Combining
eflornithine with bicalutamide may kill more tumor cells.
PURPOSE: Randomized phase II trial to compare the effectiveness of neoadjuvant eflornithine
and bicalutamide with that of eflornithine alone, bicalutamide alone, and no neoadjuvant
therapy in treating patients who are undergoing brachytherapy or radical prostatectomy for
localized prostate cancer.
- Compare levels of polyamine spermine, polyamine putrescine, and spermidine in patients
with localized prostate cancer undergoing brachytherapy or radical prostatectomy and
treated with neoadjuvant eflornithine and bicalutamide vs eflornithine alone vs
bicalutamide alone vs no neoadjuvant therapy.
- Compare the expression of surrogate biomarkers (i.e., serum prostate-specific antigen,
tissue levels of proliferating cell nuclear antigen, Ki67, and TGF-alpha, apoptosis
assays [ICH-PARP and TUNEL], and cytomorphometric indices) in patients treated with
- Compare the toxicity of these regimens in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are
stratified according to Gleason score (< 7 vs ≥ 7). Patients are randomized to 1 of 4
- Arm I: Patients receive oral eflornithine and oral bicalutamide once daily.
- Arm II: Patients receive oral eflornithine and oral bicalutamide placebo once daily.
- Arm III: Patients receive oral eflornithine placebo and oral bicalutamide once daily.
- Arm IV: Patients receive oral eflornithine placebo and oral bicalutamide placebo once
In all arms, treatment continues for 28 days in the absence of unacceptable toxicity.
Patients then undergo either prostatectomy or brachytherapy, as determined by the patient,
on day 29.
Patients are followed at 4 weeks.
PROJECTED ACCRUAL: A total of 44 patients (11 per treatment arm) will be accrued for this
study within 11 months.
- Histologically confirmed prostate cancer
- Localized disease
- Paraffin blocks from diagnostic biopsies available
- Planning to undergo brachytherapy or prostatectomy
- 18 and over
- ECOG 0-3
- Not specified
- Hemoglobin ≥ 10.0 g/dL
- WBC ≥ 3,500/mm^3
- Platelet count ≥ 125,000/mm^3
- Bilirubin ≤ 2.0 mg/dL
- SGOT and SGPT ≤ 2 times normal
- No history of liver disease (e.g., hepatitis, cirrhosis, or jaundice)
- Creatinine ≤ 2.0 mg/dL
- No symptomatic coronary artery disease
- No uncontrolled hypertension
- No acute myocardial infarction within the past year
- Fertile patients must use effective contraception
- No more than 10 decibels baseline hearing loss at any frequency by full bilateral
audiometry within the past month
- No hypersensitivity to eflornithine or bicalutamide
- No other prior or active malignancy except nonmelanoma skin cancer or other cancer
curatively treated at least 5 years ago with no evidence of recurrent or residual
- No concurrent acute or chronic medical or psychiatric condition that would preclude
PRIOR CONCURRENT THERAPY:
- No concurrent immunotherapy
- No other concurrent chemotherapy
- More than 1 year since prior antiandrogen, luteinizing hormone-releasing hormone
(LHRH) agonist, bicalutamide, finasteride, or diethylstilbestrol
- No other concurrent antiandrogen, LHRH agonist, finasteride, or diethylstilbestrol
- See Disease Characteristics
- No other concurrent radiotherapy
- See Disease Characteristics