Mitoxantrone, Etoposide, and Vinorelbine As Second-Line Therapy in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy

OBJECTIVES:

Primary

• Determine the palliative response rate in patients with hormone-resistant prostate cancer treated with mitoxantrone hydrochloride vs etoposide vs vinorelbine ditartrate as second-line therapy.

Secondary

• Determine the duration of palliative response in patients treated with these regimens.
• Determine the biological response (PSA > 50%) in these patients.
• Determine the time to progression (biological and clinical) in these patients.
• Determine the overall survival of these patients.
• Determine the quality of life and the impact on autonomy of patients over 70 years of age.
• Determine the toxicity of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive mitoxantrone hydrochloride IV over 5 minutes once a week for 3 weeks.
• Arm II: Patients receive oral etoposide twice daily on days 1-14.
• Arm III: Patients receive oral vinorelbine ditartrate once daily on days 1 and 8 and oral prednisone once daily on days 1-21.

Treatment in all three arms repeats every 3 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Metastatic progressive disease meeting the following criteria:

• Increase in measurable lesions > 25%
• Increase in bone lesions > 25%
• Biological progression rate of PSA > 4 ng/mL
• Received docetaxel as first-line chemotherapy
• Received at least 1 prior regimen of hormone therapy
• Pain > 2 on Visual Analog Scale or continuing level 2 analgesics
• No symptomatic or evolutionary CNS disease

PATIENT CHARACTERISTICS:

• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times normal
• Alkaline phosphatase ≤ 2 times normal (unless bone metastases are present)
• Transaminases ≤ 1.5 times normal
• Bilirubin ≤ 1.5 times normal
• No prior malignancy except basal cell skin cancer
• No peripheral neuropathy or severe neuropathy ≥ grade 2
• No other severe lung, hepatic, renal, or digestive disease that would be complicated by treatment
• LVEF > 50%
• No history of peptic ulcer, unstable diabetes, or other contraindication to using steroids
• No severe infection requiring antibiotics

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 8 weeks since prior metabolic radiotherapy
• More than 4 weeks since prior external radiotherapy
• At least 1 month since prior docetaxel-based chemotherapy
• At least 1 month since prior antiandrogen therapy in the case of complete hormonal blockage
• No participation in another clinical trial within the past 30 days