Liposomal Doxorubicin and Thermal Therapy in Treating Patients With Prostate Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of doxorubicin HCl liposome released through thermal microwave therapy in patients with adenocarcinoma of the prostate.
• Determine the pharmacokinetics and biodistribution profile of this drug in these patients.
• Determine the safety profile and dose-limiting toxicity of this drug in these patients.
• Determine the clinical response in patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive doxorubicin HCl liposome IV over 30 minutes. Patients then undergo a 60-minute course of prostate thermotherapy. Treatment may repeat every 28-42 days for up to 6 courses, at the discretion of the physician.

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

Patients are followed at 8, 15, 30, and 90 days.

PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Rising prostate-specific antigen AND radiographic evidence of extraprostatic prostate cancer by bone scan, CT scan, prostascint scan, or MRI

PATIENT CHARACTERISTICS:

Age

• 40 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 4,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10.0 g/dL

Hepatic

• Bilirubin normal
• AST normal
• Alkaline phosphatase normal
• No acute or chronic liver disease

Renal

• Creatinine less than 1.5 times upper limit of normal

Cardiovascular

• Ejection fraction at least 50% by MUGA
• EKG normal
• No myocardial infarction or cerebral vascular accident within the past 6 months
• No life threatening cardiac arrhythmias
• No congestive heart failure
• No cardiac pacemaker
• No peripheral arterial disease with intermittent claudication or Leriches syndrome (i.e., claudication of the buttocks or perineum)

Other

• Fertile patients must use effective barrier contraception during and for 3 months after study participation
• No sperm donation during and for 3 months after study participation
• Not febrile
• No interest in future fertility or fathering children
• No significantly decreased pain response
• No severe urethral stricture
• No protruding median lobe resulting in a "ball-valve" type of obstruction at the bladder neck
• No major psychiatric illness that would prevent informed consent
• No major psychiatric illness that required inpatient treatment within the past 3 months
• No psychological, family, sociological, or geographic condition that would preclude study compliance
• No allergy to eggs or egg products
• No urinary or prostatic infection
• No full urinary retention
• No penile or urinary sphincter implant
• No metallic implants in the pelvic or femoral area
• No other serious medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent live vaccines

Chemotherapy

• No prior anthracycline
• No concurrent streptozocin

Endocrine therapy

• No concurrent hormonal therapy (except luteinizing hormone-releasing hormone analog)
• No concurrent glucocorticoids administered at more than physiologic replacement doses (other than as an antiemetic)

Radiotherapy

• Not specified

Surgery

• More than 3 months since prior major surgery

Other

• No prior therapy that resulted in permanent reduction of pain response (e.g., prior surgery, regional or local anesthetic)
• No concurrent PC-SPES
• No concurrent cyclosporine, phenobarbital, or phenytoin