Docetaxel, Androgen Ablation Therapy, and External-Beam Radiation Therapy in Treating Patients With High-Risk Localized Prostate Cancer

OBJECTIVES:

Primary

- Determine the dose-limiting toxicity and maximum tolerated dose of docetaxel when
administered in combination with androgen ablation therapy and adaptive external-beam
radiotherapy in patients with high-risk localized adenocarcinoma of the prostate.

Secondary

- Determine the 2-year biochemical progression-free survival of patients treated with
this regimen.

OUTLINE: This is a multicenter, open-label, dose-escalation study of docetaxel.

- Androgen ablation therapy: Patients receive leuprolide acetate or other luteinizing
hormone-releasing hormone agonist beginning 2-3 months prior to the start of
chemoradiotherapy and continuing for up to 2 years.

- Chemoradiotherapy: Patients receive docetaxel IV over 1 hour on day 1 and high-dose
external-beam radiotherapy on days 1-5. Treatment repeats every 7 days for 8 courses in
the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed every 3 months.

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- High-risk localized disease, meeting 1 of the following criteria:

- T3 or T4

- T1-2 with Gleason score 8-10

- T1-2 with Gleason score 7 AND PSA ≥ 10 ng/mL

- T1-2 with any Gleason score AND PSA ≥ 20 ng/mL

- No evidence of metastatic disease on chest x-ray, bone scan, or CT scan of the
abdomen and pelvis

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 10 years

- Absolute neutrophil count ≥ 1,500/mm^3

- Hemoglobin ≥ 8.0 g/dL

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1.2 mg/dL

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 1.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study therapy

- No peripheral neuropathy > grade 1

- No myocardial infarction or significant change in anginal pattern within the past
year

- No New York Heart Association class II-IV congestive heart failure

- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80

- No other invasive malignancy within the past 5 years except for carcinoma in situ or
nonmelanoma skin cancer

- No concurrent uncontrolled illness, psychiatric condition, or other condition that
would preclude study treatment

PRIOR CONCURRENT THERAPY:

- No prior pelvic or prostate radiotherapy for prostate cancer

- No prior chemotherapy for prostate cancer

- Prior androgen ablation therapy with luteinizing hormone-releasing hormone agonists
allowed provided study treatment is started within 3 months of the initiation of
androgen ablation therapy

- No other concurrent investigational agents

- Concurrent anticoagulation with stable dose of warfarin or low molecular weight
heparin allowed