Chemotherapy, Hormone Therapy, and Radiation Therapy in Treating Patients With Locally Advanced Prostate Cancer

OBJECTIVES:

- Determine the feasibility and safety of paclitaxel, estramustine, carboplatin, and
androgen ablation followed by radiotherapy in patients with poor-prognosis locally
advanced prostate cancer.

- Determine the progression-free survival and time to prostate specific antigen failure
in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 1 hour once weekly; oral estramustine three times a day,
five days a week; and carboplatin IV over 1 hour once monthly. Treatment repeats every 4
weeks for 4 courses.

Patients also receive gonadotropin-releasing hormonal therapy comprising either goserelin
subcutaneously or leuprolide intramuscularly once monthly. Treatment repeats every 4 weeks
for 6 courses.

After the completion of chemotherapy, patients undergo radiotherapy once daily on weeks
17-24.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1.5 years.

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate with one of the following
prognostic factors:

- Tx N0, baseline prostate specific antigen (PSA) greater than 20 ng/mL, and
Gleason score at least 7

- T3b-4 N0, any baseline PSA, and any Gleason score

- No pelvic lymph node disease requiring pelvic radiotherapy

- No metastatic disease by bone scan, CT scan, or MRI

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

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

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

Hepatic:

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- SGOT no greater than 1.5 times ULN

Renal:

- Creatinine no greater than 1.5 times ULN

Cardiovascular:

- No significant cardiovascular disease

- No New York Heart Association class III or IV congestive heart failure

- No active angina pectoris

- No myocardial infarction within the past 6 months

- No history of hemorrhagic or thrombotic cerebral vascular accident

- No deep vein thrombosis within the past 6 months

Pulmonary:

- No pulmonary embolism within the past 6 months

Other:

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior immunotherapy for prostate cancer

- No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy:

- No prior chemotherapy for prostate cancer

- No other concurrent anticancer chemotherapy

Endocrine therapy:

- No more than 6 weeks of prior androgen deprivation therapy

- No other concurrent anticancer hormonal therapy except steroids for adrenal failure
and/or hormones for nondisease-related conditions (e.g., insulin for diabetes)

Radiotherapy:

- See Disease Characteristics

- No prior radiotherapy for prostate cancer

- No other concurrent anticancer radiotherapy

Surgery:

- At least 4 weeks since prior major surgery

Other:

- No prior alternative therapy (e.g., PC-SPES) for prostate cancer

- No concurrent alternative medicine (e.g., PC-SPES or saw palmetto) or large
quantities of vitamins

- No other concurrent anticancer therapy