S9921, Hormone Therapy With or Without Mitoxantrone and Prednisone in Patients Who Have Undergone Radical Prostatectomy for Prostate Cancer

OBJECTIVES:

- Compare the overall and disease-free survival of patients with high-risk adenocarcinoma
of the prostate treated with adjuvant androgen deprivation therapy with or without
mitoxantrone and prednisone after radical prostatectomy.

- Compare the qualitative and quantitative toxic effects of these regimens in this patient
population.

- Compare the prostate-specific antigen (PSA) progression-free survival rate in patient
treated with these regimens.

- Determine whether PSA progression is a surrogate endpoint for survival or disease-free
survival in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
surgical extent of disease (organ confined vs not organ confined, but N0 vs N1), Gleason's
sum (less than 7 vs 7 vs greater than 7), and planned radiotherapy (yes vs no). Patients are
randomized to one of two treatment arms.

- Arm I:Patients receive goserelin subcutaneously once every 13 weeks (8 injections total)
and oral bicalutamide once daily for 2 years in the absence of disease progression or
unacceptable toxicity.

- Arm II:Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone
twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence
of disease progression or unacceptable toxicity. Patients also receive hormonal therapy
as in arm I beginning concurrently with the initiation of mitoxantrone and prednisone.

Patients may undergo radiotherapy 5 days a week for 6.5-7.8 weeks beginning anytime (arm I)
or after completion of chemotherapy (arm II), at the discretion of the physician, in the
absence of disease progression or unacceptable toxicity.

Patients are offered the possibility to participate in biomarker research by allowing their
tissue/blood to be studied.

Patients are followed every 6 months for 2 years and then annually for up to 13 years.

PROJECTED ACCRUAL: A total of 1,360 patients (680 per treatment arm) will be accrued for this
study within 9.5 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed stage T1-T3 adenocarcinoma of the prostate before radical
prostatectomy and lymph node dissection

- Must have undergone prostatectomy within the past 120 days

- Must meet at least 1 of the following pathologic criteria:

- Gleason sum at least 8

- pT3b (seminal vesicle), pT4, or N1

- Gleason sum of 7 and positive margin

- Preoperative PSA greater than 15 ng/mL, Gleason score greater than 7, or PSA
level greater than 10 ng/mL and Gleason score greater than 6

- Must have an undetectable PSA (no greater than 0.2 ng/mL) documented after surgery or
prior to adjuvant hormonal therapy (for patients initiating adjuvant hormonal therapy
prior to study)

- No evidence of metastatic disease on bone scan if PSA is 20 ng/mL or greater at
clinical diagnosis

- No distant metastatic disease

PATIENT CHARACTERISTICS:

Performance status:

- SWOG 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Not specified

Renal:

- Not specified

Cardiovascular:

- No uncontrolled congestive heart failure

- If history of cardiac disease, LVEF at least 50% by MUGA scan or 2-D echocardiogram

Other:

- No HIV positivity

- No other prior malignancy within the past 5 years except adequately treated basal cell
or squamous cell skin cancer or stage I or II cancer that is currently in complete
remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- Not specified

Endocrine therapy:

- Prior neoadjuvant hormonal therapy of no more than 4 months duration before radical
prostatectomy allowed

- Other concurrent adjuvant hormonal therapy allowed if initiated prior to study

- Concurrent low-dose megestrol (less than 40 mg/day) for hot flashes allowed

Radiotherapy:

- No prior radiotherapy

- No concurrent whole pelvis irradiation

- Concurrent radiotherapy allowed at the discretion of the physician

Surgery:

- See Disease Characteristics

- See Endocrine therapy

- Recovered from prior surgery

Other:

- No other prior or concurrent therapy for adenocarcinoma of the prostate