RATIONALE: Drugs used in chemotherapy, such as flavopiridol, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop tumor cells from dividing so they stop growing or die. Flavopiridol may also make tumor cells more sensitive to chemotherapy. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of flavopiridol when given together with oxaliplatin, fluorouracil, and leucovorin in treating patients with advanced solid tumors.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of flavopiridol when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine, preliminarily, the therapeutic activity of this regimen in these patients.

Secondary

• Determine the dose-limiting toxicity and the recommended phase II dose of flavopiridol when administered with this regimen in these patients.
• Determine the safety and tolerability of this regimen in these patients.
• Correlate p21, p53, and apoptotic markers with response in patients treated with this regimen.

OUTLINE: This is a non-randomized, open-label, dose-escalation study of flavopiridol.

Patients receive flavopiridol IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of flavopiridol 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. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose.

PROJECTED ACCRUAL: A total of 3-46 patients will be accrued for this study within approximately 2 years.

• Drug: alvocidib
• Drug: fluorouracil
• Drug: leucovorin calcium
• Drug: oxaliplatin

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor

  • Refractory to standard therapy or no standard therapy exists
• Evaluable disease

• No known untreated CNS metastases

  • Patients who have undergone local treatment for brain metastases and whose brain metastases are stable by repeat imaging study performed ≤ 4 weeks after treatment are allowed
• No primary CNS tumors

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,500/mm^3
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for liver metastases)

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No cardiac arrhythmias within the past 6 months
• No congestive heart failure within the past 6 months
• No myocardial infarction within the past 6 months
• No arterial or venous thrombosis within the past year

Other

• No peripheral neuropathy > grade 1
• No other medical condition that would preclude study participation
• No serious or uncontrolled infection
• HIV negative

• Not pregnant or nursing

  • No nursing during and for 2 months after study participation
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 2 weeks since prior immunotherapy

Chemotherapy

• At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
• No prior flavopiridol

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior radiotherapy

Surgery

• Not specified

Other

• Recovered from all prior therapy

• No concurrent therapy for thrombosis

  • Prophylaxis for central lines or deep vein thrombosis allowed
• No other concurrent investigational medications

• No concurrent vitamins, antioxidants, or herbal preparations and supplements

  • Concurrent single-tablet multivitamin allowed