Polyunsaturated Fatty Acids in Treating Patients With Prostate Cancer Undergoing Prostate Biopsy and/or Surgery

OBJECTIVES:

- Compare fatty acid analysis of red blood cells, levels of eIF2α phosphorylation, and
tumor differentiation grade, as measured by Gleason score, in patients undergoing
prostate biopsy. (Part 1)

- Determine if neoadjuvant n-3 polyunsaturated fatty acids (PUFAs) induce phosphorylation
of eIF2α in these patients. (Part 2)

- Compare eIF2α phosphorylation, Gleason score, and the time to prostate-specific antigen
failure in prostate tumor samples obtained from the Gelb Center of the Dana-Farber
Cancer Institute prostate tissue repository. (Part 3)

OUTLINE: This is a prospective study, followed by a randomized, double-blind,
placebo-controlled study, followed by a retrospective study.

- Part 1: Patients undergo tumor biopsy and blood sample collection at baseline. Samples
are analyzed by gas-liquid chromatography for determination of n-3 and n-6
polyunsaturated fatty acid (PUFA) red cell membrane concentrations. Biopsy samples are
analyzed for eIF2α phosphorylation by immunohistochemistry. Some patients proceed to
part 2.

- Part 2: Patients undergo blood sampling as in part 1 with additional tumor and blood
collection on day 28. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral n-3 PUFAs (fish oil) once daily for 28 days prior to
tumor resection.

- Arm II (control): Patients receive oral n-6 PUFAs (corn oil) once daily for 28 days
prior to tumor resection.

- Part 3: Tumor samples and associated pathology data (Gleason score) and clinical data
(PSA values and patient's outcome) are obtained from a prostate tissue repository at the
Gelb Center of the Dana-Farber Cancer Institute. Samples are analyzed to correlate eIF2α
phosphorylation, Gleason scores, and time to PSA failure.

PROJECTED ACCRUAL: A total of 600 patients and 1,000 stored tissue samples will be accrued
for this study.

Inclusion Criteria:

- Men undergoing an outpatient prostate biopsy independently indicated by a physician.

- Patients will be selected from the population initially studied with a prostate biopsy
for possible prostate cancer

- sub-group without evidence of cancer

- sub-group with advanced prostate cancer beyond the currently accepted criteria
for surgical treatment,

- sub-group with indication of radical prostatectomy

- Patients will be recruited from the population of patients from Brigham and Women's
Hospital for surgery referred from other institutions/doctors where their biopsy was
taken and the diagnosis of prostate cancer was originally made. These patients are not
eligible for Aim 1 but will enter the randomized trial (Aim 2 with baseline)

Exclusion Criteria:

- Prostate biopsy patients who do not accept and sign an informed consent form to

- donate ten ml of blood for fatty acid analysis in red blood cells

- allow their prostate biopsy to be analyzed as discarded pathological material

- authorize access to their hospital clinical information for follow up studies

- Patients with a current diagnosis of a condition that might interfere with the
measurements of fatty acids in red blood cell membranes such as severe anemia (less
than 9g/100m1% hemoglobin

-- Or

- Diseases of lipid metabolism such as familial dyslipoproteinemia, liver cirrhosis,
advanced renal failure, and malabsorption syndrome.

- Exclude from this study patients from (indication of radical prostatectomy) who refuse
the surgical recommendation or schedule surgery at a location other than Brigham and
Women's Hospital.

- Patients who are not able to complete the full program will not be taken into
consideration in the final data analysis.