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 and giving drugs in different ways may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of surgery followed by floxuridine plus systemic fluorouracil and leucovorin in treating patients with liver metastases from colorectal cancer.

OBJECTIVES:

• Evaluate the efficacy of hepatic resection followed by portal vein infusion of floxuridine plus systemic fluorouracil/leucovorin calcium in patients with metastatic colorectal cancer.
• Study the toxic effects of adjuvant chemotherapy following hepatic resection.
• Evaluate mRNA expression of enzymes that may be important to the cytotoxicity of fluoropyrimidines in tumor cells, including thymidylate synthase, ribonucleotide reductase, and folylglutamyl synthetase, by polymerase chain reaction and immunohistochemistry.

OUTLINE: Following resection of the liver and all extrahepatic colorectal cancer, patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks.

If biopsy-proven metastatic disease develops, treatment may be stopped at the investigator's discretion. Continuation of regional therapy should be considered for extrahepatic failure. No concurrent radiotherapy is permitted.

Patients are followed every 3 months for 3 years, then every 6 months for survival.

PROJECTED ACCRUAL: It is expected that 50 patients will be entered over approximately 5 years.

• Colorectal Cancer
• Metastatic Cancer

• Drug: floxuridine
• Drug: fluorouracil
• Drug: leucovorin calcium
• Procedure: adjuvant therapy
• Procedure: conventional surgery

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal carcinoma or radiologically confirmed colorectal carcinoma in a synchronous metastasis

• Intrahepatic metastases required

  • No more than 15 metastases involving no more than 60% of functioning liver

• No extrahepatic disease unless:

  • Resectable anastomotic or locally recurrent tumor
  • Resectable mesenteric lymph node involvement in patients undergoing initial resection of primary colorectal carcinoma
  • Disease extension from liver metastasis amenable to en bloc resection (e.g., diaphragm wall, kidney, abdominal wall)
• No biopsy-proven chronic active hepatitis

PATIENT CHARACTERISTICS:

Age:

• Physiologic 18 to 70

Performance status:

• Karnofsky 60%-100%

Hematopoietic:

• AGC at least 1,500
• Platelets at least 100,000

Hepatic:

• Bilirubin no greater than 2.0 mg/dL (unless reversibly obstructed by metastasis)

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• No second malignancy within 5 years except adequately treated:

  • Nonmelanomatous skin cancer
  • In situ bladder cancer
  • In situ cervical cancer
  • No pregnant women

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Prior mitomycin or nitrosoureas allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the liver
• At least 3 weeks since radiotherapy and recovered
• Prior pelvic radiotherapy allowed
• No planned concurrent radiotherapy

Surgery:

• Not specified