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 compare the effectiveness of fluorouracil plus leucovorin with that of no further therapy in treating patients who have stage II or stage III colon cancer that can be surgically removed.

Condition	Treatment or Intervention	Phase
stage II colon cancer stage III colon cancer	Drug: fluorouracil  Drug: leucovorin calcium	Phase III

Further Study Details: 

OBJECTIVES: I. Compare survival, disease free survival, and locoregional and distant metastases recurrence rates of patients with stage IIC or stage III colon cancer treated with curative colon resection with or without perioperative fluorouracil, followed by fluorouracil and leucovorin calcium. II. Compare survival and disease free survival in patients with stage IIB colon cancer treated with curative colon resection with or without perioperative fluorouracil.

PROTOCOL OUTLINE: This is a randomized study. Patients undergo curative colon resection via laparotomy. Patients are randomized to 1 of 2 arms. Arm I: Within 24 hours of the colon resection, patients receive perioperative fluorouracil IV over 24 hours for 7 days. Arm II: 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 reregistered 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 fluorouracil 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 fluorouracil and leucovorin calcium. Patients are followed every 3 months for 2 years, then every 6 months for 2 years, and then annually.

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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Adenocarcinoma of the colon documented by colonoscopy or barium enema
• Tumor either considered resectable or totally resected within 24 hours prior to study
• No dual primary tumors
• 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 E-3293 strongly recommended

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior fluorouracil; No other prior or concurrent chemotherapy for this malignancy
• Endocrine therapy: Not specified
• Radiotherapy: No prior or concurrent radiotherapy for this malignancy
• Surgery: See Disease Characteristics

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Hematopoietic: WBC at least 3,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 2.0 mg/dL
• Renal: Creatinine no greater than 2.0 mg/dL
• Other: No prior nonmalignant systemic disease that would preclude use of chemotherapy; No second malignancy within 5 years except: Superficial nonmelanomatous skin cancer; Carcinoma in situ of the cervix; Not pregnant or nursing; Fertile patients must use adequate contraception

Illinois
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States

Study chairs or principal investigators

Robert L. Comis,  Study Chair,  Eastern Cooperative Oncology Group   
Charles A. Coltman, Jr.,  Study Chair
Richard L. Schilsky,  Study Chair
Norman Wolmark,  Study Chair
Francis Joseph Harford, Jr.,  Study Chair

Study ID Numbers:  CDR0000078337; E-1292; INT-0136
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002525
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08