RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon-gamma may interfere with the growth of tumor cells and slow the growth of the tumor. Combining more than one drug with interferon-gamma may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving fluorouracil together with phenylbutyrate, indomethacin, and interferon-gamma and to see how well it works in treating patients with stage IV colorectal cancer.

OBJECTIVES:

• Determine the maximum tolerated dose of fluorouracil administered with phenylbutyrate, indomethacin, and interferon gamma in patients with advanced colorectal adenocarcinoma.
• Determine the toxic effects of this regimen in these patients.
• Determine the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of fluorouracil (5-FU).

• Phase I:Patients receive 5-FU IV over 24 hours on day 1; phenylbutyrate IV over 120 hours and oral indomethacin daily on days 2-6; and interferon gamma subcutaneously on days 2, 4, and 6. Courses repeat weekly in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 5-FU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which less than 2 of 6 patients experience dose-limiting toxicity (DLT).

• Phase II :Patients receive 5-FU, phenylbutyrate, indomethacin, and interferon gamma as in phase I at the MTD.

Patients are followed for survival.

PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for the phase I portion of this study and approximately 46 patients will be accrued for the phase II portion of this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV colorectal adenocarcinoma
• Bidimensionally measurable disease on x-ray, CT scan, or MRI required for phase II patients
• No brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 16 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)

Renal:

• Creatinine no greater than 2 times ULN

Cardiovascular:

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

Nutritional:

• Adequate oral intake
• No diarrhea

Other:

• No other serious concurrent illness
• No dependence on immunosuppressive drugs, including corticosteroids

• No other malignancy within the past 5 years except:

  • Inactive nonmelanoma skin cancer
  • Carcinoma in situ of the cervix
  • Grade I bladder cancer
• No allergy to interferon gamma or E. coli-derived products
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for metastatic disease
• At least 12 months since prior adjuvant chemotherapy

Endocrine therapy

• No concurrent corticosteroids

Radiotherapy

• At least 12 months since prior adjuvant radiotherapy

Surgery

• Not specified

Other

• No concurrent immunosuppressive drugs