Combination Chemotherapy With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for High Risk Stage II or Stage III Colon Cancer

Inclusion Criteria

• Signed written informed consent obtained prior to any study specific screening procedures.
• Patient willing and able to comply with the protocol.
• Age ≥ 18 years-of-age.
• Histologically confirmed colon carcinoma, American Joint Cancer Committee/Union Internationale Contre le Cancer (AJCC/UICC) Stage II or Stage III defined as a tumor location ≥ 15 cm from the anal verge by endoscopy or above the peritoneal reflection at surgery. The patient was not to be a candidate for (neo) adjuvant radiotherapy. Note: Stage II patients were to be considered as high-risk patients fulfilling one of the following criteria:
• T4 tumours,
• Patients presenting with bowel obstruction or perforation,
• Histological signs of vascular invasion (i.e. blood and lymphatic vessels) or perineural invasion,
• Patients aged less than 50 years,
• Patients with sub-optimal surgery (less than 12 nodes analyzed).
• Curative surgery not less than 4 and not more than 8 weeks prior to randomization.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy of ≥ 5 years.

Exclusion Criteria

• Macroscopic or microscopic evidence of remaining tumour. Patients should never have had any evidence of metastatic disease (including presence of tumour cells in the ascites). The isolated finding of cytokeratin positive cells in bone marrow is not considered evidence of metastatic disease for purposes of this study.
• Carcinoembryonic antigen > 1.5 x upper limit of normal (ULN) after surgery (during screening period).
• For patients with colostomy, unwilling to delay revision until at least 28 days after treatment completion.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, not fully healed wounds, or anticipation of the need for major surgical procedure during the course of the study. Any central venous access device (CVAD) for chemotherapy administration must be inserted at least 2 days prior to treatment start.
• Previous anti-angiogenic treatment for any malignancy; cytotoxic chemotherapy, radiotherapy or immunotherapy for colon cancer.
• Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
• Females with a positive or no pregnancy test (within 7 days before treatment start) unless childbearing potential can be otherwise excluded (postmenopausal i.e. amenorrheic for at least 2 years, hysterectomy or oophorectomy).
• Lactating women.
• Fertile women ( 150/100 mmHg) while receiving chronic medication, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, clinically significant electrocardiogram (ECG) findings (e.g. QTc ≥ 440 msecs [male] 460 msecs [female] or ≥ 2º atrioventricular block, etc.).

Patients who suffer from serious cardiac arrhythmia requiring medication can enter the study only if they are considered to be in a stable condition regarding both the arrhythmia and their medication. Patients with pacemakers are allowed to enter the study only if they are considered as being in a stable condition. In case of doubt, the investigator should obtain a consultation with a local cardiologist.

• Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication.
• Interstitial pneumonia or extensive symptomatic fibrosis of the lungs.
• Known peripheral neuropathy ≥ Common terminology criteria for adverse events (CTCAE) version 3.0 Grade 1. Absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible.
• Organ allografts requiring immunosuppressive therapy.
• Serious, non-healing wound, ulcer, or bone fracture.
• Evidence of bleeding diathesis or coagulopathy.
• Current or recent (within 10 days prior to study treatment start) us