RATIONALE: Drugs used in chemotherapy such as perifosine use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of perifosine in treating patients who have prostate cancer that no longer responds to androgen ablation therapy.

OBJECTIVES:

• Determine the 4-month progression-free survival rate, as measured by prostate-specific antigen and clinical criteria, in patients with metastatic androgen-independent prostate cancer treated with perifosine.
• Determine the side-effect profile of this drug in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.

OUTLINE:

• Course 1: Patients receive oral perifosine twice on day 1 and once daily on days 2-21.
• All subsequent courses: Patients receive oral perifosine once daily on days 1-21.

In all courses, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 22-46 patients will be accrued for this study within approximately 1.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate, meeting all of the following criteria:

  • Metastatic
  • Androgen-independent
  • Progressive disease while continuing to receive hormonal ablation (e.g., luteinizing hormone-releasing hormone [LHRH] agonist)

• Progression documented by at least 1 of the following parameters:

  • Two consecutively rising prostate-specific antigen levels, at least 1 week apart, with at least 1 measurement that is 50% above the nadir reached after the last treatment regimen (as long as the last measurement is at least 5 ng/mL)
  • At least 1 new metastatic lesion on technetium Tc 99m bone scintigraphy

  • Progression of soft-tissue metastases as measured by appropriate modalities (i.e., imaging or palpation) and demonstrated by at least 1 of the following:

    • Development of new area of malignant disease (measurable or nonmeasurable)
    • At least a 20% increase in the sum of the longest diameters (LD) of target lesions from the smallest sum of LD recorded since the treatment started or the appearance of 1 or more new lesions
• Patients who have not undergone surgical castration must have a testosterone level less than 50 ng/mL and continue on their LHRH agonist during study treatment
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin less than 1.0 mg/dL or upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No unstable or newly diagnosed angina pectoris
• No New York Heart Association class II-IV congestive heart failure

Ophthalmic

• No pre-existing retinal disease
• No pathologic baseline electrooculogram

Other

• Fertile patients must use effective barrier contraception
• Able to ingest oral medication
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to perifosine (e.g., miltefosine or edelfosine)
• No ongoing or active infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance
• No other active malignancies within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the bladder

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No more than 1 prior chemotherapy regimen
• More than 4 weeks since prior chemotherapy (at least 6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• See Disease Characteristics
• More than 4 weeks since prior flutamide
• More than 6 weeks since prior bicalutamide or nilutamide

Radiotherapy

• At least 6 weeks since prior bone-seeking radioisotopes
• Recovered from prior radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• Recovered from any acute toxicity related to prior therapy
• More than 3 months since prior UCN-01
• More than 3 months since prior suramin
• No concurrent commercial or other investigational agents or therapies intended to treat the malignancy
• No concurrent combination antiretroviral therapy for HIV-positive patients