Pre- and Postoperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer

Inclusion Criteria:

* Patients with histologically confirmed diagnosis of metastatic CRC including potentially resectable liver metastases, untreated yet with chemotherapy for metastatic disease
* At least one measurable metastatic lesion (as per RECIST criteria)
* Prior adjuvant or neo-adjuvant chemotherapy/radiotherapy allowed
* ECOG performance status 0 or 1
* Signed written informed consent
* life expectancy greater than 3 months
* patients below 18 years of age
* Adequate haematological function: White blood count ≥ 3 x 1000/L with neutrophils ≥ 1.5 x 1000/L, platelet count ≥ 100 x 1000/L, and hemoglobin ≥ 5.6 mmol/L (9g/dL)
* Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) range, alkaline phosphatase, Aspartate aminotransferase (ASAT) and Alanin aminotransferase (ALAT) ≤ 5 x ULN
* Serum creatinine ≤ 1.25 ULN and/or creatinine clearance ≥ 60 ml/min
* Urine dipstick of proteinuria \<2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate 1 g of protein/24 hr
* INR ≤ 1.5 and PTT ≤ 1.5 x ULN within 7 days prior to enrolment
* Women of childbearing potential must have a negative serum pregnancy test done 1 week prior to the administration of the study drug. She and her partner should prevent pregnancy (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) up to at least 6 months after last treatment completion or the last drug dose, whatever happens first.
* Patient must be able to comply with the protocol

Exclusion Criteria

* Extrahepatic disease, except concurrent diagnosis of primary CRC
* Prior chemotherapeutic treatment for metastatic CRC
* Serious, non healing wound, ulcer, or bone fracture.
* Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment,
* Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
* Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication
* Pregnancy (absence to be confirmed by ß-HCG test) or lactation
* Men of childbearing potential not willing to use effective means of contraception
* Previous exposure to anti-VEGF antibodies
* Treatment with any investigational agent(s) within 4 weeks prior to study entry
* Known allergic/hypersensitivity reaction to any of the components of study treatments
* Clinically significant cardiovascular disease, for example CVA (6 months before treatment start), myocardial infarction (6 months before treatment start), unstable angina, NYHA grade 2 CHF, or uncontrolled hypertension.
* History of significant neurologic or psychiatric disorders including dementia, seizures, bipolar disorder
* Medical or psychological condition that would not permit the patient to complete the study or sign informed consent
* Known alcohol or drug abuse
* Clinical or radiological evidence of CNS metastases.
* Past or current history (within the last 2 years prior to treatment start) of other malignancies except metastatic colorectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).
* History of thromboembolic or haemorrhagic events within 6 months prior to treatment.
* Evidence of bleeding diathesis or coagulopathy
* Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes i.e. except for anticoagulation for maintenance of patency of permanent indwelling IV catheters.
* Chronic daily treatment with aspirin (\> 325 mg/day) or clopidogrel (\>75 mg/day).
* Chronic daily treatment with corticosteroids (dose of 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
* Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial
* gastrointestinal ulceration
* Known peripheral neuropathy NCI CTC Grade 1. Absence of deep tendon reflexes (DTRs) as the sole neurological abnormality does not render the patient ineligible