PS-341 in Treating Patients With Advanced Cancer

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.

Eligibility Criteria:
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