The use of preoperative chemoradiation and adjuvant chemotherapy with 5-FU based chemotherapy reduced local recurrence rate to less than 10%, but has only had limited effect on overall survival due to the constantly high (more than 30%) rate of distant metastasis.

However, it has been shown that complete eradication of the primary tumour observed in the histopathological specimen (pathological complete response, pCR) correlates with a favourable overall prognosis so obtaining a pCR might be beneficial. The aim of the study is to investigate whether the addition of bevacizumab to preoperative fluoropyrimidinebased chemoradiation improves pathological complete remission rate in locally advanced rectal cancer with acceptable toxicity. Secondary objectives are to evaluate pathological downstaging rate, histopathological R0 resection rate,sphincter preservation rate, perioperative surgical complication rate, local control, DFS, OS, late toxicity and quality of life.

• radiotherapy: 45 Gy to the pelvis (25x 1.8 Gy on days 1-33, excluding weekends) plus 5.4 Gy on days 36-38 as a boost to the primary tumour (3 fractions of 1.8 Gy).Three- dimensional CT planing and a four field box technique with high energy photons (15 MV) will be used. All fields will be treated daily. Multileaf collimators will be used to shape individual radiation fields. Patients will be irradiated in a prone position with a full bladder and by using belly board to minimize exposure of the small bowel.
• capecitabine 825 mg/m² p.o. twice daily on days 1-38 (including weekends),
• bevacizumab: at dose 5 mg/kg on days -14, 2, 16,30.
• Radical surgery (TME): to be undertaken ideally 6-8 weeks following completion of chemoradiation.

Postoperative treatment (in patients achieving histopathological R0 or R1 resection):capecitabine 1250 mg/m² p.o. twice daily for 14 consecutive days every three weeks; 4 cycles (R0)or 6 cycles (R1) beginning 6-8 weeks after surgery

Inclusion Criteria:

• Male or female patients with histologically proven adenocarcinoma of the rectum (tumour located below the peritoneum), T3/4 or any node positive disease (clinical stage according the TNM classification system)
• No evidence of metastatic disease.
• The disease must be considered either resectable at the time of entry or thought to become resectable after preoperative chemoradiation.
• Age 18 - 80 years
• WHO Performance Status 0-2
• No prior radiotherapy, chemotherapy or any targeting therapy for rectal cancer
• Adequate hematological, hepatic and renal function Ability to swallow tablets
• Signed informed consent
• Patients must be willing and able to comply with the protocol for duration of the study

Exclusion Criteria:

• Malignancy of the rectum other than adenocarcinoma
• Any unrested synchronous colon cancer
• Other co-existing malignancy or malignancy within the past 5 years, with the exception of adequately treated in situ carcinoma of the cervix or basal cell carcinoma of the skin
• Significant heart disease (uncontrolled hypertension despite of medication (> 150/100 mmHg), NYHA class III or IV heart disease,unstable angina or myocardial infarction within the past 1 year prior the study entry, history of significant ventricular arrhythmia requiring treatment)
• Serious, non-healing wound, ulcer or bone fracture
• Evidence of active peptic ulcer or upper GI bleeding
• Evidence of bleeding diathesis or coagulopathy
• Chronic daily treatment with high-dose aspirin(>325mg/day)
• Current or recent (>10 days) use of full-dose of parenteral anticoagulants or thrombolytic agents for therapeutic purpose
• Patients receiving a concomitant treatment with drugs interacting with capecitabine such as flucitosine, phenytoin, or warfarin
• Known dihydropyrimidine dehydrogenase (DPD)deficiency
• Major surgery within 4 weeks prior to study treatment starts, or lack of complete recovery from the effects of major surgery or open biopsy
• Known hypersensitivity to biological drugs
• Treatment with any investigational drug within 30 days before beginning treatment with the study drug
• Pregnant or lactating patient
• Females with a positive or no pregnancy test unless childbearing potential can be otherwise excluded (amenorrheic for at least 2 years,hysterectomy or oophorectomy)