The study was stopped before reaching its accrual goal due to slow accrual

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. It is not yet known if surgery is more effective with or without chemotherapy for colon cancer.

PURPOSE: Randomized phase III trial to evaluate whether perioperative 5-Fluorouracil (5-FU) chemotherapy after curative resection could improve overall survival and disease-free survival in patients with Duke's B3 or C colon cancer.

OBJECTIVES:

I. To determine if adjuvant therapy with one week of continuous 5-FU given within 24 hours of a curative colon resection followed by 6 months of 5-FU/leucovorin is effective in prolonging the disease-free survival and increasing overall survival in patients with Dukes' B3 or C colon cancer, when compared to patients who are treated with 5-FU/leucovorin only.

II. 1. To determine if a week of perioperative continuous 5-FU affects disease-free survival and overall survival in patients with Dukes' B2 colon cancer.

OUTLINE: This is an open-label, randomized phase III study. Patients undergo curative colon resection via laparotomy. Patients are randomized to 1 of 2 arms in a 1:1 ratio.

Arm I (Perioperative 5-FU): Within 24 hours of the colon resection, patients receive perioperative 5-fluorouracil (5-FU) intravenously (IV) over 24 hours for 7 days.

Arm II (No perioperative 5-FU): Patients receive no perioperative fluorouracil.

After surgery, patients with stage I, stage IIA, or stage IV colon cancer are immediately removed from study. Patients with stage IIB, IIC, or III colon cancer are re-registered within 35 days postoperatively. Beginning 21-35 days after surgery, patients with stage IIC or III disease receive leucovorin calcium IV bolus immediately followed by 5-FU IV bolus on days 1-5. Courses repeat every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stage IIB disease do not receive adjuvant 5-FU and leucovorin calcium.

Patients are followed every 3 months for 2 years, then every 6 months for 2 years, and then annually until 15 years.

PROJECTED ACCRUAL: A total of 800-2,000 patients (at least 400 per treatment arm) will be accrued for this study over 2-3 years.

Eligibility Criteria for Randomization:

Inclusion Criteria:

• Adenocarcinoma of the colon documented by colonoscopy or barium enema

• Tumor either considered resectable or totally resected within 24 hours prior to study

• Randomization within 2 weeks prior to surgery or within 24 hours after surgery required

• Patients randomized after surgery must meet the following criteria:

  • Complete resection performed with no evidence of residual disease or distant metastases
  • Distal margin of tumor above the peritoneal reflection in area of rectum
  • No free perforation Intestinal obstruction allowed
  • Preliminary or complementary colostomy allowed

• Concurrent registration for E3293 strongly recommended

• Age 18 and over

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Adequate organ function based on the following tests within 2 weeks prior to randomization

  • White Blood Cell (WBC) at least 3,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 2.0 mg/dL
  • Creatinine no greater than 2.0 mg/dL

• No second malignancy within 5 years except: superficial non-melanomatous skin cancer and carcinoma in situ of the cervix

• Fertile patients must use adequate contraception

Exclusion Criteria:

• Dual primary tumors
• Prior nonmalignant systemic disease that would preclude use of chemotherapy
• Pregnant or nursing
• Prior fluorouracil
• Other prior or concurrent chemotherapy for this malignancy
• Prior or concurrent radiotherapy for this malignancy

Eligibility Criteria for Re-registration for Patients Randomized Pre-operatively:

• Must have pathologic classification of Dukes' B2, B3, or C disease by the contributing institution.
• Must be re-registered < 35 days after surgery.
• ECOG performance status of 0-2.
• Complete resection must have been performed with no evidence of residual disease or distant metastasis.
• Distal margin of the tumor must not extend below the peritoneal reflection in the area of the rectum.
• Single primary colon carcinoma without free perforation demonstrated. Patients with intestinal obstruction are eligible. Preliminary or complementary colostomy dose not preclude entry of a patient.
• Have WBC > 3000/mm^3, platelets > 100,000/mm^3, adequate renal (serum creatinine <= 2.0mg/dL) and hepatic function (bilirubin <= 2.0mg/dL), within one week prior to beginning adjuvant chemotherapy (For Dukes' B3 and C patients only).

Eligibility Criteria for Re-registration for Patients Randomized Post-operatively:

• Must have pathologic classification of Dukes' B2, B3, or C disease by the contributing institution.
• Patient must be re-registered < 35 days after surgery.
• ECOG performance status of 0-2.
• Started perioperative 5-FU, if assigned, within 24 hours of surgery.
• Have WBC > 3000/mm^3, platelets > 100,000/mm^3, adequate renal (serum creatinine <= 2.0mg/dL) and hepatic function (bilirubin < =2.0mg/dL), within one week prior to beginning adjuvant chemotherapy (For Dukes' B3 and C patients only).

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

The primary analysis population for the study was all randomized patients with Duke's B3 and C disease.

Patients on Arm I received perioperative 5-FU, patients on Arm II received no perioperative chemotherapy. AEs, however, were reported for all patients and assessed at the end of treatment and 30 days after the last dose of the therapy.

After completion of perioperative 5-FU, patients with Dukes' B3/C disease continued to receive the then standard adjuvant chemotherapy for colon cancer. AEs for the adjuvant chemotherapy (5-FU+ Levamisolem and 5-FU+Leucovovin) in patients with Dukes' B3/C disease were collected separately and reported here as well.