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