A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer Patients

Inclusion Criteria: 1. Histologically-confirmed colorectal carcinoma 2. Stage IV or recurrent colorectal cancer 3. age ≥ 20 years 4. ECOG performance status ≤1 5. At least one measurable tumor mass according to RECIST 1.1 6. Expected survival for approximately 12 weeks or longer 7. No prior systemic chemotherapy 8. At least 4 weeks later after surgery or radiotherapy 9. At least 12 months after adjuvant chemotherapy Exclusion Criteria: 1. Prior statins therapy within 1-year from the date of study entry 2. Prior chemotherapeutic treatment for metastatic colorectal cancer. 3. Prior other anti-VEGF (vascular endothelial growth factor) or TKIs (Tyrosine kinase inhibitors) treatment 4. Current, Known CNS(central nervous system) malignancy (history of completely resected or irradiated brain metastases by WBRT (whole-brain radiation therapy) or stereotactic radiosurgery allowed. 5. Severe or unstable cardiac disease, including (for example) coronary artery disease requiring increased doses of anti-anginal medication and/or coronary angioplasty (including stent placement) within the preceding 24 months(congestive heart failure NYHA (New York Heart Association) III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias) 6. Past or current history (within the last 5 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) 7. Uncontrolled systemic illness such as DM (diabetes mellitus), hypertension, hypothyroidism and infection 8. History of thromboembolic or hemorrhagic events within 6 months prior to treatment 9. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to enrollment. 10. Evidence of bleeding diathesis or coagulopathy