Perifosine in Treating Patients With Metastatic, Androgen-Independent Prostate Cancer

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.

Eligibility Criteria:
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