Combination Chemotherapy Followed by Surgery in Treating Patients With Localized Prostate Cancer

OBJECTIVES:

- Determine the 5-year freedom from prostate-specific antigen (PSA) recurrence in
patients treated with this regimen.

- Define the maximum tolerated dose of neoadjuvant docetaxel and mitoxantrone followed by
prostatectomy in patients with high-risk localized prostate cancer. (Phase I completed
as of 2/15/02)

- Determine the toxicity of this regimen in these patients.

- Determine the PSA response rate and pathologic response rate in patients treated with
this regimen.

- Determine the clinical response in patients treated with this regimen.

- Determine the overall survival of patients treated with this regimen.

- Determine the surgical margin status at time of prostatectomy in patients treated with
this regimen.

OUTLINE: This is a dose-escalation study of mitoxantrone. (Phase I completed as of 2/15/02)

Patients receive neoadjuvant docetaxel and mitoxantrone weekly on weeks 1-3. Treatment
repeats once a week for a total of 4 courses.

Patients receive escalating doses of mitoxantrone until the maximum tolerated dose is
determined. (Phase I completed as of 2/15/02)

Patients undergo prostatectomy 2-4 weeks after completion of neoadjuvant chemotherapy.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- High-risk, as defined by 1 of the following:

- Stage T2b (palpable bilateral involvement) or surgically resectable T3

- PSA 15 ng/mL or greater

- Gleason grade greater than 4+3 (4+3, 4+4, or 5+any, but not 3+4)

- At least a 50% chance of prostate cancer recurrence within 5 years

- Planned prostatectomy as primary therapy

- No evidence of bone metastases by bone scan

- No evidence of lymph nodes greater than 2 cm on pelvic computed tomography (CT) scan
(scan required only if PSA greater than 40 ng/mL)

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Eastern Cooperative Oncology Group(ECOG) 0-2

Life expectancy:

- At least 10 years

Hematopoietic:

- White Blood Cell(WBC) at least 3,000/mm^3

- Neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Conjugated bilirubin no greater than upper limit of normal (ULN)

- Alkaline phosphatase no greater than 4 times ULN

- Alanine transaminase(ALT) no greater than 2 times ULN (1.5 times ULN if alkaline
phosphatase greater than 2.5 times ULN)

Renal:

- Not specified

Cardiovascular:

- Ejection fraction greater than 50% by Multiple Gated Acquisition(MUGA)scan

Other:

- No other malignancy within the past 5 years except nonmelanoma skin cancer

- No significant active medical illness that would preclude study therapy

- No peripheral neuropathy grade 2 or greater

- No hypersensitivity to drugs formulated with polysorbate-80

- No significant contraindications to corticosteroids

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No prior cytotoxic chemotherapy

- No other concurrent cytotoxic chemotherapy

Endocrine therapy:

- No prior or concurrent conventional hormonal therapy

Radiotherapy:

- No prior or concurrent radiotherapy (external beam or brachytherapy)

Surgery:

- See Disease Characteristics

Other:

- No prior or concurrent cryotherapy