1. The distal extent of the tumor must be > 12 cm from the anal verge on endoscopy. If the patient is not a candidate for endoscopy, then the distal extent of the tumor must be > 12 cm from the anal verge as determined by surgical examination.

2. Patients must have paraffin-embedded tumor specimen available for evaluation of microsatellite instability and loss of heterozygosity at 18q, to determine high risk versus low risk. Tumor samples will be shipped as specified in Section 10.2. High-risk patients will be randomized to treatment Arms A or B. Low-risk patients will be registered to Arm C for observation. (Criteria noted in Sections 3.2.1 through 3.2.18 need not be met.) NOTE: Every effort should be made to submit blocks to the PCO immediately. Blocks CANNOT be accepted after day 50 (post surgery) in order to allow for molecular assessment.

3. Patients must have no history of isolated, distant, or non-contiguous intra-abdominal metastases, even if restricted.

4. Patients must have histologically confirmed adenocarcinoma of the colon that meets the criteria below: Stage II carcinoma (T3,4 N0 M0): The tumor invades through the muscularis propria into the subserosa or into non-peritonealized pericolic or perirectal tissues (T3) or directly invades other organs or structures and/or perforates visceral peritoneum (T4). Appendix IV provides TNM nomenclature and staging for colon cancer.

5. Patients must have > 8 lymph nodes evaluated and reported.

6. Patients must not have presented with complete obstruction or perforation of the bowel.

7. Patients must not have had any systemic or radiation therapy initiated for this malignancy.

8. Patients with prior malignancies, including colorectal cancers, are eligible if they have been disease-free for > 5 years and are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years prior to randomization.

9. Patients must be > 18 years old.

10. Patients must have ECOG performance status of 0-2.



Step 2: Randomization (High Risk Patients ? Arms A and B only)

1. Within 2 weeks prior to randomization, postoperative absolute granulocyte count (AGC) must be > 1500/mm3 (or < 1500/mm3, if in the opinion of the investigator, this represents an ethnic or racial variation of normal).

2. Within 2 weeks prior to randomization, the postoperative platelet count must be > 100,000/mm3.

3. Within 2 weeks prior to randomization, there must be postoperative evidence of adequate hepatic function. Bilirubin must be < ULN unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin. Alkaline phosphatase must be < 2.5 x ULN. AST must be < 1.5 x ULN. If alkaline phosphatase or AST is > than above limits, serologic testing for Hepatitis B and C must be obtained and results must be negative.

4. Within 2 weeks prior to randomization, there must be postoperative evidence ofadequate renal function. Serum creatinine < 1.5 x ULN. Urine protein/creatinine (UPC) ratio of < 1.0. Patients with a UPC ratio > 1.0

must undergo a 24-hour urine collection, which must be an adequate collection

and must demonstrate < 1 gm of protein in order to participate. (See Appendix

VIII).

5. Patients with any significant bleeding that is not related to the primary colon tumor within 6 months prior to study entry are not eligible.

6. Patients with gastroduodenal ulcer(s) determined to be active by endoscopy are not eligible.

7. Patients with a history of hypertension must measure <150/90 mmHg and be on a stable regimen of anti-hypertensive therapy.

8. Patients must not have a serious or non-healing wound, skin ulcers or bone fracture.

9. Patients receiving concomitant halogenated antiviral agents are not eligible.

10. Patients experi