RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have metastatic or unresectable solid tumors.

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of bortezomib in combination with leucovorin calcium and fluorouracil in patients with advanced solid tumors.
• Determine the pharmacodynamics of bortezomib, in terms of 20S proteasome and NFkB inhibition, in patients treated with this regimen.
• Determine the objective tumor response in these patients.
• Determine the correlation between 20S proteasome and NFkB inhibition and clinical toxicity in these patients.
• Determine the pharmacokinetics of fluorouracil in combination with bortezomib in these patients.

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

Patients receive bortezomib IV on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) 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.

PROJECTED ACCRUAL: A total of 15 to 30 patients will be accrued for this study within 1 year.

• Drug: bortezomib
• Drug: fluorouracil
• Drug: leucovorin calcium

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic or unresectable solid tumor not amenable to standard therapy
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than normal
• AST/ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No EKG evidence of acute ischemia or significant conduction abnormality
• No history of cardiac or cerebrovascular disease due to hypotension and tachycardia

Other

• No other concurrent uncontrolled illness
• No ongoing or active 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 immunotherapy and recovered

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

Surgery

• At least 2 weeks since prior major surgery

Other

• No other concurrent investigational agents
• No concurrent antiretroviral therapy (HAART) for HIV