Liver Infusions of Fluorouracil in Treating Patients With Dukes' A, Dukes' B, or Dukes' C Colon Cancer Undergoing Surgery

OBJECTIVES: Determine whether adjuvant therapy with portal hepatic perfusion of 5-fluorouracil and sodium heparin effectively prolongs the disease-free interval and increases survival in patients undergoing curative resection of adenocarcinoma of the colon.

OUTLINE: Randomized study. Patients are randomized preoperatively; those randomized to Arm 1 begin therapy intraoperatively or within 6 hours of colonic resection. Arm 1: 5-Fluorouracil plus sodium heparin. Those randomized to Arm 2 receive no adjuvant therapy. Arm 2: observation (no further treatment).

PROJECTED ACCRUAL: 1,334 patients will be entered over a 4-year period.

Inclusion criteria

• more than one synchronous primary colon tumor
• white blood cell (WBC) > 4000/cu.mm. and platelet count greater than or equal to 100,000/cu.mm.
• evidence of adequate renal (serum creatinine less than or equal to 1.5 mg%) and hepatic function (bilirubin less than or equal to 1.5 mg%; serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 60 I.U./ml)
• performance status of 0, 1 or 2
• Patients with intestinal obstruction are eligible. Preliminary or complementary colostomy does not preclude entry of a patient provided randomization is carried out prior to the planned curative resection.
• The distal margin of the tumor must be greater than or equal to 12 cm from the anal verge as endoscopically measured with the patient in the knee-chest position.
• Carcinoembryonic antigen (CEA) must be performed pre-operatively but results need not be known at the time of randomization.

Exclusion criteria

• malignant colon tumors other than carcinoma, i.e., sarcoma, lymphoma, etc.
• patients whose tumors demonstrate free perforation
• previous or concomitant malignancy, regardless of site - except patients with squamous or basal cell carcinoma of the skin, and carcinoma in situ of the cervix which have been adequately treated
• patients who have received prior treatment other than preliminary or complementary colostomy (radiation, chemotherapy or surgery) for their current malignancy.
• patients having tumors within 12 cm of the anal verge
• performance status of 3 or 4
• patients having non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) which would preclude their being subject to the chemotherapy treatment option
• patients who are pregnant at the time of randomization
• patients with psychiatric or addictive disorders which would preclude obtaining informed consent
• patients who have multiple primary tumors involving both the colon and the rectum which would preclude them from being classified as having only colon cancer or only rectal cancer