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: Randomized phase III trial to compare the effectiveness of intravenous infusion or intrahepatic infusion of fluorouracil and leucovorin in treating patients with colorectal cancer metastatic to the liver.

OBJECTIVES: I. Compare the survival and response rates of patients with colorectal liver metastases treated with intravenous vs. intrahepatic arterial infusion of fluorouracil/leucovorin. II. Assess the effect of these 2 treatments on symptoms and quality of life of these patients.

PROTOCOL OUTLINE: Randomized study. Patients randomized to Arm II should have a preoperative hepatic angiography; at laparotomy, an intrahepatic arterial catheter is fused into the gastroduodenal artery to establish an infusion of both lobes of the liver. Arm I: Single-Agent Chemotherapy with Drug Modulation. Fluorouracil, 5-FU, NSC-19893; with Leucovorin calcium, CF, NSC-3590. Intravenous infusion. Arm II: Single-Agent Chemotherapy with Drug Modulation. 5-FU; with CF. Intrahepatic arterial infusion.

PROJECTED ACCRUAL: 312 patients are expected to be randomized within 3-4 years.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed adenocarcinoma of the colon or rectum with metastases confined to the liver and not amenable to surgery

--Prior/Concurrent Therapy--

• No prior fluorouracil (5-FU) for advanced disease; More than 6 months since adjuvant 5-FU (e.g., in AXIS or QUASAR studies)

--Patient Characteristics--

• Age: Any age
• Performance status: WHO 0-2
• Life expectancy: More than 3 months
• Hematopoietic: WBC at least 3,000/mm3; Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin less than 3.5 mg/dL (50 micromoles/liter)
• Renal: Not specified
• Cardiovascular: No uncontrolled heart disease (e.g., congestive heart failure, angina)
• Other: No uncontrolled infection; No other uncontrolled medical illness