RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of PS-341 in treating patients who have advanced cancer.

OBJECTIVES:

• Determine the maximum tolerated dose and toxicity of PS-341 in patients with advanced malignancies.
• Determine, in a preliminary manner, the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

• Regimen A: Patients receive PS-341 IV twice weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3-4 or 2 of 6 patients experience dose-limiting toxicity.

• Regimen B: Once the MTD has been determined in regimen A, patients receive PS-341 IV twice weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 14 months.

DISEASE CHARACTERISTICS:

• Histologically proven advanced malignancy, including non-Hodgkin's lymphoma (NHL), for which there is no known standard therapy that is potentially curative or definitely capable of extending life expectancy

  • Patients with B-cell lymphoproliferative disorders and a leukemic phase are eligible once the maximum tolerated dose is established

• NHL patients must meet the following conditions:

  • No greater than 25% of bone marrow involved
  • No symptomatic brain metastases
  • Prior brain metastases allowed if definitively treated (radiotherapy and/or surgery) and stable for at least 8 weeks

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2.5 times ULN (5 times ULN if liver involvement)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

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

Other:

• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy or immunotherapy
• No concurrent immunotherapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to greater than 30% of bone marrow
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No concurrent antiretroviral therapy (HAART) for HIV positive patients