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Bevacizumab plus capecitabin is a standard maintenance treatment following first-line chemotherapy in the patients with advanced colorectal adenocarcinoma. However, hand-foot syndrome induced by capecitabin will bother the patient to decrease the quality of life. S-1, an alternative of fluoropyrimidine, was proved non-inferior efficacy with lower hand-foot syndrome as first-line chemotherapy in advanced colorectal adenocarcinoma in the studies. The investigators are going to test the efficacy and safety of bevacizumab plus S-1 as maintenance treatment compared with bevacizumab plus capecitabin in colorectal adenocarcinoma

Criteria

Before the start of induction therapy:

Inclusion Criteria:

Histological proof of colorectal cancer (in case of a single metastasis, histological or cytological proof of this lesion should be obtained); Distant metastases (patients with only local recurrence are not eligible); Unidimensionally measurable disease (> 1 cm on spiral CT scan or > 2 cm on chest X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation; In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.

Ongoing or planned first line treatment with 6 cycles of Xeloda, Eloxatin, and Avastin.

Exclusion criteria Prior adjuvant treatment for stage II/III colorectal cancer ending within 6 months before the start of induction treatment Any prior adjuvant treatment after resection of distant metastases Previous systemic treatment for advanced disease

At randomisation:

Inclusion criteria:

WHO performance status 0-1 (Karnofsky PS > 70%); Disease evaluation with proven SD, PR or CR according to RECIST after 6 cycles of MTD chemotherapy performed in week 3-4 of the 6th cycle induction therapy, and randomisation performed in week 3-5 of the 6th cycle (see time table); Laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow function (Hb > 6.0 mmol/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, > 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases); Life expectancy > 12 weeks; Age >= 18 yrs; Negative pregnancy test in women with childbearing potential; Expected adequacy of follow-up; Institutional Review Board approval; Written informed consent Exclusion criteria History or clinical signs/symptoms of CNS metastases; History of a second malignancy ≤ 5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin; Previous intolerance of XelodaR, EloxatinR, and/or AvastinR for which any of these drugs have been permanently discontinued; patients with previous dose reductions or delays are eligible; patients with grade 2 neurotoxicity after the 6th cycle are eligible, and retreatment with EloxatinR after PFS1 should depend on the grade of neurotoxicity at that moment; Known dihydropyrimidine dehydrogenase (DPD) deficiency; (Planned) radical resection of all metastatic disease; Uncontrolled hypertension, i.e. consistently > 150/100 mmHg; Use of more than 3 antihypertensive drugs; Significant cardiovascular disease < 1 yr before randomisation (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism); Any of these significant cardiovascular events during previous fluoropyrimidine therapy; Chronic active infection; Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs; Any impairment of gastrointestinal function or -disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as >CTC grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow tablets); Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy; full-dose anticoagulation (is allowed if started during induction therapy); Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).