perifosine in treating patients with metastatic, androgen-independent prostate cancer

Conditions: Prostate Cancer

Summary: 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

Keywords: stage iv prostate cancer recurrent prostate cancer adenocarcinoma of the prostate