OBJECTIVES:

• Determine the dose-limiting toxicity and maximum tolerated dose of perifosine administered as a varying series of loading and maintenance doses in patients with refractory solid tumors, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, myelodysplastic syndromes, or Hodgkin's lymphoma.
• Determine the profile of adverse reactions (including changes in laboratory parameters) in patients treated with this regimen.
• Determine any disease responses that may occur in patients treated with this regimen.
• Determine the steady-state pharmacology and pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive a loading dose of oral perifosine on day 1 followed by a maintenance dose 2-3 times daily beginning on day 2 or 3 and continuing until day 21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating loading and maintenance doses of perifosine until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients are treated at that dose level.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, myelodysplastic syndromes, or Hodgkin's lymphoma that has no effective standard therapeutic option but requires systemic therapy
• No history of CNS neoplasms

• For prostate cancer:

  • Tumor progression during blockade of testicular and adrenal androgens
  • At least 4 weeks since prior flutamide or other antiandrogens without disease improvement
  • Leuprolide or other gonadotropin-releasing hormones should be maintained in patients without an orchiectomy
  • Testosterone in the castrate range

• For breast cancer:

  • At least 4 weeks since any prior hormonal therapy with evidence of disease progression

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count greater than 50,000/mm^3
• Absolute granulocyte count greater than 500/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT and SGPT no greater than 2.5 times normal

Renal:

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

Cardiovascular:

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

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No recent acute or chronic gastrointestinal conditions (e.g., stomach ulcer or enteritis) that might affect tolerability or drug absorption
• No allergic reaction to any medication with a structure similar to perifosine
• No pre-existing retinal disease or pathologic baseline electrooculogram
• No cataracts that would interfere with normal vision or require medical intervention
• No other serious concurrent illness that would preclude assessment of drug effect

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• At least 2 months since prior UCN-01
• More than 3 months since prior suramin

Endocrine therapy:

• See Disease Characteristics
• No concurrent corticosteroids except for physiological replacement or as antiemetics

Radiotherapy:

• At least 4 weeks since prior radiotherapy (6 weeks for bone-seeking radioisotopes) and recovered

Surgery:

• See Disease Characteristics

Other:

• No other concurrent antineoplastic therapies