Flutamide In the Prevention of Prostate Cancer in Patients With Neoplasia of the Prostate

OBJECTIVES: I. Determine the ability of flutamide to reduce the incidence of prostate cancer
in patients with high grade prostatic intraepithelial neoplasia. II. Determine the effect of
this regimen on a series of endpoint biomarkers in these patients. III. Assess the quality
of life of these patients.

OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients
are stratified according to age (under 65 versus 65 and over), PSA (0-2.5 versus 2.6-4.0
versus 4.1-10 versus greater than 10 ng/mL), PIN (on one biopsy versus on two biopsies), and
family history (prostate cancer in brother, father, or uncle versus no prostate cancer in
these relatives). Patients are randomized to one of two treatment arms.

DISEASE CHARACTERISTICS: Histologically confirmed high grade prostatic intraepithelial
neoplasia Confirmed by second prostate biopsy within 180 days of first biopsy No prior or
concurrent prostatic carcinoma No prior hormonal replacement or antiandrogen therapy

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy:
Greater than 5 years Hematopoietic: Not specified Hepatic: SGOT and alkaline phosphatase
no greater than 2 times upper limit of normal No hepatitis B or C or liver cirrhosis
Renal: Not specified Other: Fertile patients must use effective contraception No other
prior malignancy in past 5 years except carcinoma in situ or nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified
Endocrine therapy: See Disease Characteristics Radiotherapy: No prior radiotherapy
Surgery: Not specified