Lycopene or Omega-3 Fatty Acid Nutritional Supplements in Treating Patients With Stage I or Stage II Prostate Cancer

OBJECTIVES:

Primary

- Compare gene expression in normal prostate tissue (at baseline and after treatment) of
patients with stage I or II adenocarcinoma of the prostate treated with lycopene vs
omega-3 fatty acid nutritional supplements vs placebo.

Secondary

- Determine new candidate molecular targets for lycopene and omega-3 response pathways.

- Correlate baseline gene expression patterns, determined by cDNA array analysis, with
self-reported dietary intake.

- Correlate gene expression patterns with progression or lack of progression at 12 months
after study entry.

- Determine if lycopene or omega-3 supplements affect the incidence of tumor progression.

OUTLINE: This is a randomized, placebo-controlled study. Patients are stratified according
to dietary intake of tomato and fish (low tomato [< 4 servings/week], low fish [< 2
servings/week] vs low tomato, high fish [≥ 2 servings/week] vs high tomato [≥ 4
servings/week], low fish vs high tomato, high fish). Patients are randomized to 1 of 3
treatment arms.

- Arm I: Patients maintain normal diet and receive oral omega-3 fatty acids placebo 3
times daily and lycopene placebo twice daily.

- Arm II: Patients receive oral lycopene twice daily and oral omega-3 fatty acids placebo
3 times daily.

- Arm III: Patients receive oral lycopene placebo twice daily and oral omega-3 fatty
acids 3 times daily.

In all arms, treatment continues for up to 90 days or until post-treatment biopsy is
scheduled (a maximum of 104 days) in the absence of disease progression.

Patients complete a dietary questionnaire at baseline and then for 3 days each month during
study therapy. Quality of life is assessed at baseline and at 3 months.

Prostate tissue needle biopsies and blood samples are collected at baseline and at 3 months.
Tissue and blood samples are examined for lycopene and omega-3 fatty acids (treatment
compliance), omega-6 fatty acids, insulin-like growth factor (IGF)-1, IGF binding protein-5,
and cyclooxygenase-2 gene by polymerase chain reaction, cDNA microarray hybridization, and
other gene expression assays.

After completion of study treatment, patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 114 patients will be enrolled in this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate meeting the following
criteria:

- Newly diagnosed disease

- Small cell acinar type

- Gleason score ≤ 6 with no pattern 4 or 5 histology

- Gleason pattern 4 seen as a microfocus (< 2 mm in length) allowed

- Stage I-II (T1 or T2a) disease

- Must have had an extended pattern biopsy (defined as 8+ cores) within the past 2
years

- Patients meeting all of the eligibility criteria except for the aforementioned
extended pattern biopsy within the past two years may enroll in the study if
they have an extended pattern clinical biopsy scheduled no more than 6 weeks
before beginning study treatment AND are willing to have an additional 4 biopsy
cores

- No more than 33% of biopsy cores positive

- 33% or more of biopsy cores positive due to microfoci of adenocarcinoma allowed

- No more than 50% of the length of a tumor core involved by carcinoma

- Watchful waiting planned as primary treatment strategy

- Must have 3 serum prostate-specific antigen (PSA) level readings taken ≥ 2 weeks
apart over the past year

- PSA ≤ 10.0 ng/mL

- PSA < 15 ng/mL in patients with benign prostatic hyperplasia or prostatitis
allowed

- PSA doubling time ≥ 3 months

PATIENT CHARACTERISTICS:

- Life expectancy ≥ 3 months

- ECOG performance status 0-2

- No history of allergic reactions attributed to tomatoes, fish, soybean oil, gelatin
capsules, or compounds of similar chemical or biologic composition to lycopene
(carotenoids) or fish oil (omega-3 fatty acids)

- No uncontrolled intercurrent illness including, but not limited to, the following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

- No prior or concurrent treatment for prostate cancer, including surgery, radiation,
hormonal therapy (e.g., leuprolide acetate, bicalutamide, flutamide, goserelin,
megestrol, nilutamide, diethylstilbestrol/estrogen), chemotherapy, PC-SPES, or
investigational agents

- More than 4 weeks since prior and no concurrent lycopene, fish oil (omega-3 fatty
acids), or any other preparation intended to supplement levels of omega-3 unsaturated
fatty acids

- More than 4 weeks since prior and no concurrent finasteride, dutasteride, saw
palmetto or any other herbal/nutritional preparation indicated to affect hormone
levels

- More than 1 month since prior nonsteroidal anti-inflammatory drugs (NSAIDs),
cyclooxygenase-2 (COX-2) inhibitors, and/or aspirin for > 7 days duration

- No concurrent NSAIDs, COX-2 inhibitors, or aspirin