Patient case: 50-year-old male with prostate cancer; genetic feature: ATM deletion

Clinical trial: Perifosine in Treating Patients With Metastatic, Androgen-Independent 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.

Detailed description: 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: 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

Relevance to patient case: not relevant