SU5416 Compared to Dexamethasone in Treating Patients With Progressive Prostate Cancer That Has Not Responded to Hormone Therapy

OBJECTIVES:

• Compare the time to progression in patients with hormone refractory prostate cancer treated with dexamethasone with or without SU5416.
• Determine the differences in PSA kinetics and PSA hazard score between these two regimens in this patient population.
• Determine the objective response rate and time to development of new lesions in these patients treated with SU5416.
• Determine the toxicity of SU5416 in these patients.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral dexamethasone once a day 6 days a week. Treatment continues until disease progression, at which time patients cross over to arm II.
• Arm II: Patients receive oral dexamethasone as in arm I followed by SU5416 IV over 60 minutes twice weekly for 4 weeks. A smaller dose of dexamethasone is administered the day after SU5416. Treatment continues for a minimum of 2 courses in the absence of unacceptable toxicity or disease progression.

PROJECTED ACCRUAL: A total of 60 patients (30 per arm) will be accrued for this study within 16 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer not amenable to curative treatment with surgery or radiotherapy
• Progressive disease defined by 1 of the following criteria:

• New bone scan lesions
• New or progressive radiologic lesions
• Sequential increases in PSA on at least 2 successive measurements no less than 2 weeks apart of at least 50% above nadir on prior therapy provided absolute value at time of enrollment is at least 5 ng/mL
• Progressive disease, as defined above, despite adequate hormonal therapy defined by all of the following:

• Continued treatment with an LHRH agonist or prior orchiectomy
• Sequential or concurrent treatment with an antiandrogen (e.g., flutamide, nilutamide, or bicalutamide)
• Trial of antiandrogen withdrawal at least 4 weeks prior to study
• CNS metastasis allowed if:

• Previously treated
• Neurologically stable
• Oral or intravenous steroids or anticonvulsants not required
• Brain scan (CT or MRI) within the past 2 weeks shows no active or residual disease

• Negative brain scan required if neurologic signs or symptoms suggestive of CNS metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No uncompensated coronary artery disease
• No history of myocardial infarction or severe unstable angina within the past 6 months
• No severe peripheral vascular disease associated with diabetes mellitus
• No deep venous or arterial thrombosis within the past 3 months

Pulmonary:

• No pulmonary embolism within the past 3 months

Other:

• Not pregnant
• Fertile patients must use effective contraception
• No significant uncontrolled underlying medical or psychiatric illness
• No serious active infection
• No other prior or concurrent malignancy except nonmelanoma skin cancer unless completed therapy and considered to be at less than 30% risk of relapse
• No history of severe allergic or anaphylactic reactions to paclitaxel or docetaxel

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy
• No other concurrent chemotherapy
• No other concurrent investigational antineoplastic drugs

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior major surgery