FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer

Inclusion Criteria:

• Histologically confirmed AJCC/UICC high-risk stage II or stage III colon cancer .High-risk stage III patients (T4, N+, M0, or any T, N2, M0) may also be furtherrandomized in the BEV study (plus or minus BEV)

• Stage II patients have to be considered at high-risk if they fulfill >1 of thefollowing criteria:

• T4 tumours,

• grade >3,

• clinical presentation with bowel obstruction or perforation,

• histological signs of vascular or lymphatic or perineural invasion,

• <12 nodes examined

• Age 18 to 75 years

• Curative surgery no less than 3 ( 4 in the BEV study) and no more than 8 weeks priorto randomization

• ECOG performance Status (ECOG-PS) <1

• Signed written informed consent obtained prior to any study specific procedures

Exclusion Criteria:

• Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections).

• 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 cellcarcinoma of the skin and/or in situ carcinoma of the cervix)

• Lactating women

• Fertile women (<2 years after last menstruation) and men of childbearing potential notwilling to use effective means of contraception

• History of clinically relevant psychiatric disability , precluding informed consent

• Clinically relevant cardiovascular disease

• History or presence of other diseases

• Evidence of bleeding diathesis or coagulopathy

• Current or recent (within 10 days prior to study treatment start) use of full-doseoral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes

• Chronic, daily treatment with high-dose aspirin (>325 mg/day) or clopidogrel (>75mg/day)

• Current or recent (within the 28 days prior to randomization) treatment with anotherinvestigational drug or participation in another investigational study