Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

OBJECTIVES: Primary: To evaluate whether a combination of Zoladex and flutamide used as
cytoreductive agents prior to and during definitive radiation therapy improves overall
survival over radiation therapy alone in locally confined carcinomas of the prostate;
Secondary: To compare the rates of disease-specific survival, clinical relapse (local
progression and/or distant failure), freedom from prostate-specific antigen (PSA) failure,
freedom from second clinical relapse, freedom from second PSA relapse, and disease-free
survival; To compare the prostate re-biopsy at two years; To measure the effect on sexual
function.

OUTLINE: This is a randomized, multicenter study. Patients were stratified by PSA level (less
than 4 vs 4-20), tumor differentiation (well vs moderate vs poor), nodal status (N0 [nodes
evaluated by surgical sampling] vs NX [nodes evaluated negative by imaging methods only]),
and participating center. Patients are randomized to one of two treatment arms. Arm I:
Patients receive oral flutamide 3 times a day and goserelin subcutaneously once every 4
weeks, or once as a time release injection (intramuscular leuprolide may be substituted for
goserelin), beginning 2 months prior to radiotherapy and continuing until completion of
radiotherapy. Patients undergo radiotherapy daily 4-5 days per week for almost 8 weeks. Arm
II: Patients undergo radiotherapy only, as in arm I. Patients are followed every 3 months for
the remainder of the first year, every 4 months for the second year, every 6 months for the
third through fifth years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1980 patients within 5 years.

Inclusion criteria:

- Histologically confirmed locally confined adenocarcinoma of the prostate with primary
tumors confined to the prostate, clinical stage T1b,1c, 2a or 2b.

- Negative nodes evaluated by imaging methods (classified in the study as NX) or by
surgical sampling (classified in the study as N0).

- Karnofsky performance status ≥ 70.

- PSA is mandatory, must be ≤ 20)

- No prior hormonal therapy, radiation or chemotherapy.

- Prior finasteride for prostate hypertrophy allowed if discontinued at least 60 days
prior to randomization.

- Prior testosterone administration allowed if at least 90 days elapsed since last
administration.

- No evidence of distant metastasis or other synchronous primary. Patients with prior
invasive malignancy who were disease free for at least 5 years could be eligible with
pre-randomization approval by the study chairman.

- Treatment begins within 21 days after randomization.

- Patients signs a study-specific informed consent form.

- Alanine Aminotransferase (ALT) within 2x upper normal limits.

Exclusion criteria:

- Stage T1a or ≥ T2c disease.

- Lymph node involvement (N1 - N3).

- Evidence of distant metastasis. (M1)

- PSA > 20.

- Radical surgery or cryosurgery for carcinoma of the prostate, previous irradiation,
antiandrogen therapy or chemotherapy.

- Previous or concurrent cancers other than basal cell or squamous cell skin carcinoma.

Patients with squamous cell carcinomas required to be NED (no evidence of disease) for a
minimum of two years prior to study entry.

- Major medical or psychiatric illness which, in the investigator's opinion, would
prevent completion of treatment and would interfere with follow-up.

- Karnofsky performance status of < 70.