RATIONALE: Suberoylanilide hydroxamic acid may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I trial to study the effectiveness of suberoylanilide hydroxamic acid in treating patients who have advanced cancer.

OBJECTIVES:

• Determine the maximum tolerated dose of suberoylanilide hydroxamic acid in patients with advanced solid tumors or hematologic malignancies.
• Evaluate the pharmacokinetic profile of this drug in these patients.
• Determine the effects of this drug on absorption in the fasting and non-fasting states in these patients.
• Determine any anti-tumor effects of this drug in these patients.
• Correlate clinical outcomes with histone acetylation in circulating mononuclear cells and tumor biopsy samples in patients treated with this drug.

OUTLINE: This is a dose-escalation study. Patients are stratified according to disease (solid tumor vs multiple myeloma or lymphoma vs leukemia or myelodysplastic syndromes).

The initial 15-20 patients (in the solid tumor or multiple myeloma or lymphoma stratum) receive suberoylanilide hydroxamic acid (SAHA) IV over 2 hours on day 1 of week 0 and then orally once or twice daily beginning on day 1 of week 1. All remaining patients receive oral SAHA once or twice daily beginning on day 1 of week 1. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

In each stratum, cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed monthly for resolution of adverse events.

PROJECTED ACCRUAL: A maximum of 114 patients (42 with solid tumors, 36 with lymphoma or multiple myeloma, and 36 with leukemia or myelodysplastic syndromes) will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • Histologically confirmed advanced primary or metastatic solid tumor, including, but not limited to, the following:

    • Androgen-independent prostate cancer
    • Breast cancer
    • Ovarian cancer
    • Head and neck cancer
    • Non-small cell lung cancer
    • Bladder cancer
    • Kidney cancer

  • Diagnosis of lymphoma, multiple myeloma, leukemia, or myelodysplastic syndromes (MDS), including, but not limited to, the following:

    • Intermediate-grade or follicular non-Hodgkin's lymphoma
    • Hodgkin's lymphoma
• Patients with lymphoma or multiple myeloma must be ineligible for peripheral blood stem cell transplantation

• For patients with solid tumors (except prostate cancer):

  • Disease progression based on development of new lesions or an increase in pre-existing lesions
  • Biochemical marker increase must not be sole criterion for disease progression

• For prostate cancer patients only:

  • Disease progression based on rising prostate-specific antigen (PSA) values, transaxial imaging, or radionuclide scans
  • Increase in disease-related symptoms must not be sole manifestation of progression
  • Patients receiving an antiandrogen as part of first-line hormonal therapy must show disease progression off of the antiandrogen prior to study

  • Biochemical progression (at least 25% increase over range of values) defined as 1 of the following:

    • Rising PSA documented by at least 3 consecutive measurements obtained at least 1 week apart
    • Rising PSA documented by at least 2 consecutive measurements obtained more than 1 month apart

  • PSA at least 4 ng/mL

    • Testosterone no greater than 50 ng/mL
    • If no prior orchiectomy, must maintain castrate levels of testosterone
• Disease must be refractory to standard therapy or for which no curative therapy exists
• No active CNS or epidural tumors

• Hormone receptor status:

  • Not specified NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3 (patients with solid tumors)
• Platelet count greater than 25,000/mm^3 (patients with hematologic malignancy)
• Absolute neutrophil count at least 500/mm^3 (patients with hematologic malignancy)

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN
• PT no greater than 15 seconds

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No New York Heart Association class III or IV heart disease

Pulmonary

• No severe debilitating pulmonary disease

Other

• No infection requiring IV antibiotics
• No other severe medical problems that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• At least 4 weeks since prior chemotherapy

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior ketoconazole
• At least 2 weeks since prior steroids for patients with lymphoma
• Concurrent gonadotropin-releasing hormone analogs or diethylstilbestrol to maintain castrate levels of testosterone allowed for prostate cancer patients
• No concurrent ketoconazole

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy to sole measurable lesion

Surgery

• See Disease Characteristics
• No concurrent surgery

Other

• Recovered from all prior therapy
• At least 4 weeks since prior palliative therapy for solid tumor patients with progressive metastatic disease (if present)
• At least 4 weeks since prior investigational anticancer therapeutic drugs
• At least 2 weeks since prior conventional cytotoxic therapy for patients with leukemia or MDS
• At least 4 weeks since prior investigational therapy for patients with leukemia or MDS
• No other concurrent investigational drugs
• No other concurrent anticancer agents