OBJECTIVES:

• Compare immunologic response, as measured by the increase in prostate-specific antigen (PSA)-specific T-cell precursors, in patients with localized prostate cancer treated with vaccine comprising recombinant vaccinia-PSA and rV-B7.1 plus recombinant fowlpox-PSA vaccine, sargramostim (GM-CSF), and low-dose interleukin-2 (IL-2) vs no vaccine regimen.
• Determine the safety and tolerability of this regimen in combination with radiotherapy in these patients.
• Compare the toxic effects of IL-2 in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to planned radiotherapy (irradiation alone vs irradiation and radioactive implant) and planned hormonal therapy (yes vs no). Patients are randomized to treatment arms I or II and, once accrual on these arms is complete, up to 20 patients (9-10 HLA-A2 positive) are accrued to arm III.

• Arm I: Patients receive vaccine comprising recombinant vaccinia-PSA admixed with rV-B7.1 subcutaneously (SC) on day 2. On days 30, 58, 86, 114, 142, 170, and 198, patients receive recombinant fowlpox-PSA vaccine SC. Beginning on day 86, patients undergo radiotherapy 5 days a week with total duration dependent upon whether patient undergoes radiotherapy alone or radiotherapy plus brachytherapy. Patients receive sargramostim (GM-CSF) SC on days 1-4, 29-32, 57-60, 85-88, 113-116, 141-144, 169-172, and 197-200. Patients receive low-dose interleukin-2 SC on days 8-12, 36-40, 64-68, 91-95, 120-124, 148-152, 176-180, and 204-208.
• Arm II: Patients undergo radiotherapy 5 days a week with total duration dependent upon whether patient undergoes radiotherapy alone or radiotherapy plus brachytherapy.
• Arm III: Patients undergo radiotherapy and receive recombinant vaccinia-PSA admixed with rV-B7.1 vaccine and GM-CSF as in arm I. Patients also receive a lower dose of IL-2 SC on days 8-21, 36-49, 64-77, 91-104, 120-133, 148-161, 176-189, and 204-217.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 13 years.

PROJECTED ACCRUAL: A total of 48-49 patients (19 for arm I, 11 for arm II, and 18-19 for arm III) will be accrued for this study within 10-15 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed localized adenocarcinoma of the prostate that has not undergone local therapy
• Must be a candidate for definitive radiotherapy and agree to be treated with external beam radiotherapy alone or in combination with brachytherapy
• HLA-A2 positive (arms I and II and at least 9 patients accrued to arm III)
• Prior vaccinia immunization required

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-1 OR
• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute lymphocyte count at least 600/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 1.6 mg/dL
• AST and ALT no greater than 4 times normal
• No hepatic dysfunction that may be exacerbated by interleukin-2 (IL-2)

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min
• No abnormal urinalysis (proteinuria less than 150 g/24 hours) unless cause is non-renal
• No concurrent renal disease that may be exacerbated by IL-2

Cardiovascular:

• No concurrent cardiac disease that may be exacerbated by IL-2

Pulmonary:

• No concurrent pulmonary disease that may be exacerbated by IL-2

Immunologic:

• HIV negative
• No history of allergy or adverse reaction to prior vaccinia vaccine
• No known allergy to eggs
• No active infection requiring antibiotics (including chronic suppressive therapy)
• No active or prior eczema or other eczematoid skin disorders
• No acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• No altered immune function

• No autoimmune disease, including any of the following:

  • Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
  • Systemic lupus erythematosus
  • Sjögren's syndrome
  • Scleroderma
  • Myasthenia gravis
  • Goodpasture's syndrome
  • Addison's disease
  • Hashimoto's thyroiditis
  • Active Graves' disease

Other:

• No other serious illness
• No other malignancy within the past 3 years except basal cell or squamous cell skin cancer
• No prior seizures, encephalitis, or multiple sclerosis

• No close household contact with the following individuals for at least two weeks after vaccinia inoculation:

  • Individuals with active or prior eczema or other eczematoid skin disorders
  • Individuals with acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves
  • Children under age 5
  • Pregnant or nursing women
  • Immunodeficient or immune-suppressed individuals by disease or therapy, including HIV infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• Not specified

Endocrine therapy:

• Concurrent hormonal therapy allowed
• No concurrent glucocorticoids
• No concurrent dexamethasone or other corticosteroids as antiemetics

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to more than 50% of nodal groups

Surgery:

• No prior disease-related surgery
• No prior splenectomy

Other:

• At least 3 days since prior antibiotics