Radiation Therapy, Docetaxel, and Hormone Therapy in High-Risk Locally Advanced Metastasized Prostate Cancer

OBJECTIVES:

Primary

• Determine, preliminarily, the grade III or IV toxicity rate of concurrent extended-field intensity-modulated radiotherapy (IMRT), docetaxel, and androgen deprivation therapy in patients with high-risk, locally advanced prostate cancer with pelvic lymph node metastasis.

Secondary

• Determine, preliminarily, the progression-free survival of patients treated with this regimen.
• Determine the maximum tolerated dose of docetaxel when administered with concurrent IMRT in this patients.

OUTLINE: This is a dose-escalation study of docetaxel.

Patients receive combined androgen deprivation therapy (if not already on combined hormonal therapy) comprising goserelin acetate* subcutaneously once every 3 months for up to 2 years and oral bicalutamide once daily beginning on day 1 and continuing until the completion of radiotherapy. Beginning at approximately week 9 of androgen deprivation therapy, patients receive docetaxel IV over 1 hour once weekly for up to 9 weeks. Concurrently with chemotherapy, patients undergo intensity-modulated radiotherapy 5 days a week for up to 45 fractions (9 weeks).

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.

Note: *Not required for patients who have undergone bilateral orchiectomy

After completion of study therapy, patients are followed periodically for 5 years.

Inclusion criteria

• Histologically confirmed adenocarcinoma of the prostate

o Locally advanced disease (T1 -T3b, N1 or N2, M0) at high risk for recurrence

• Biopsy-proven pelvic lymph node involvement
• No T4 lesion
• Prior androgen suppression within the past 14 months is allowed provided the following criterion is met:

o No biochemical evidence of PSA progression after androgen withdrawal

• PSA progression, defined as 2 consecutive rising PSA values > 4.0 ng/mL taken ≥ 2 weeks apart
• Karnofsky performance status 80-100%
• absolute neutrophil count (ANC) ≥ 1,500/mm³
• Hemoglobin ≥ 10 g/dL
• Platelet count > 100,000/mm³
• Bilirubin normal
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
• Meets 1 of the following criteria:
• Alkaline phosphatase (AP) normal and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 5 times upper limit of normal (ULN)
• AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
• AP ≤ 5 times ULN AND AST or ALT normal

Exclusion criteria

• No evidence of distant metastasis, including any of the following:

• Bone metastasis
• Pathologic or radiographic evidence of lymph node involvement above the L4 - L5 interspace
• No peripheral neuropathy > grade 1
• No significant comorbidity that would preclude radiotherapy
• No other prior malignancy except nonmelanoma skin cancer or any other cancer for which the patient has been disease-free for the past 5 years
• No hypersensitivity to docetaxel or other drugs formulated with polysorbate 80
• No history of Crohn's disease, ulcerative colitis, or irritable bowel syndrome
• No unrepaired inguinal hernia
• No prior pelvic or abdominal radiotherapy or prostate brachytherapy implant
• No prior prostatectomy
• No prior pelvic or abdominal surgery that resulted in excessive amounts of small intestine located within the pelvis
• No other concurrent investigational agents