Hormone Therapy in Treating Patients With Prostate Cancer

RATIONALE: Male hormones can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide and finasteride may fight prostate cancer by reducing the production of male hormones.

PURPOSE: Phase II trial to study the effectiveness of flutamide and finasteride in treating prostate cancer patients with high PSA levels who were previously treated with radiation therapy or radical prostatectomy.

OBJECTIVES:

* Determine the efficacy of finasteride and flutamide in suppressing prostate specific antigen (PSA) levels in patients with elevated PSA after definitive radiation therapy or radical prostatectomy for prostate cancer.
* Assess sexual function and other quality of life issues during this therapy.
* Estimate the response to flutamide withdrawal in this group of patients who have not had a major reduction in circulating testosterone levels.
* Measure the response rate to further hormonal manipulation with combined androgen blockade after the failure of this therapy.
* Obtain data that may predict more aggressive disease.

OUTLINE: This is a multicenter study.

Patients receive finasteride and flutamide by mouth three times a day. Patients experiencing recurrence or a greater than 4 nu/mL (above 50%) increase in PSA level will discontinue flutamide treatments. Otherwise, patients continue therapy in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed prior to therapy and at 3 and 6 months.

Patients are followed every 3 months for one year and every 6 months thereafter.

PROJECTED ACCRUAL: This study will accrue 100 patients over 2 years.

Eligibility Criteria:
1. Histologic Documentation: Previous histologic evidence of adenocarcinoma of the prostate.
2. Prior Treatment:

   2.1 Definitive Local Therapy: Patients must have had a previous attempt at definitive therapy, which is defined as a previous radical prostatectomy or radiation therapy with at least 5500 cGy to the prostate.
   1. Patients may have had both radiation therapy to the prostate and surgical resection, given as definitive therapy, provided they began the radiation therapy within 3 months of their prostatectomy. Also, brachytherapy alone and combinations of brachytherapy and external beam radiation therapy are also allowed, if given as a single therapy, and not given for a rising PSA after the previous therapy.
   2. The previous treatment must have occurred at least 6 months, but no more than 10 years, prior to registration.

   2.2 Previous Hormonal Therapy or Other Treatments: Patients may have had no more than 6 months of hormonal therapy with their other treatment, and must have been off all hormones used for the treatment of prostate cancer including Megace for at least 12 months.
   1. No therapy within 2 years with finasteride or other 5 alpha-reductase inhibitors.
   2. No previous chemotherapy for this malignancy.
   3. No orchiectomy.
   4. No corticosteroids in excess of standard replacement doses for adrenal failure.
3. Elevated PSA Criteria:

   3.1 Patients must a PSA level between 1 ng/ml and 10 ng/ml, with a rise of at least 1 ng/ml above the nadir produced by definitive therapy. The PSA level must be repeated at least once, one month later to confirm the rise of 1 ng/ml above nadir.

   3.2 After the second PSA has been drawn to confirm the rise, one additional PSA should be drawn as close to the start of therapy as possible. Therefore, a total of three PSAs must be drawn prior to the start of therapy. Only the last two need to be drawn at the same lab (ie, the second confirmatory PSA and the PSA drawn just prior to the start of the trial). The nadir PSA and the initial PSA suggesting a rise can be drawn at outside laboratories. The combination of the nadir PSA and the two PSAs showing a rise of 1.0 ng/ml are used for determining eligibility. The two elevated PSAs must be at least one month apart.
4. No clear evidence of local recurrence on the digital rectal exam.
5. No metastatic disease on the CT or bone scan.
6. Performance status 0-2
7. Required initial laboratory data

   1. SGOT and/or SGPT ≤2 x upper limits of normal
   2. Creatinine ≤2 x upper limits of normal
   3. Bilirubin ≤2 x upper limits of normal