Neo-adjuvant Therapy and the Effect on Synchronous Metastatic Growth

Study Hypothesis • As well as in animal models as in patients with colorectal cancer resection of the primary tumor resulted in increase in vascular density, metabolism and secondary tumor growth of the distant metastases. These data strongly suggest an inhibitory effect of the primary tumor on the outgrowth of its metastases. In this study we investigate whether pre-operative treatment with the anti-angiogenic agent bevacizumab and/or chemotherapy before resection of the primary colorectal tumor shifts the balance between angiogenic and anti-angiogenic factors in favor of the anti-angiogenic factors and results in reduced growth of the liver metastases. Eligibility * Histological proven colorectal cancer without signs of bowel obstruction or bleeding * Synchronous liver metastases * WHO performance status 0-1 Treatment * Arm A: immediate surgery of the primary colorectal tumor, no neoadjuvant therapy * Arm B: neoadjuvant treatment with bevacizumab during 7 weeks prior to surgery of the colorectal primary * Arm C: neoadjuvant treatment with CAPOX during 7 weeks prior to surgery of the colorectal primary * Arm D: neoadjuvant treatment with bevacizumab and CAPOX during 7 weeks prior to surgery of the colorectal primary Primary endpoint Difference in response of liver metastases to resection of the primary tumor between the experimental groups and the control group, as determined by histopathological scoring of vascular density, apoptotic and mitotic index and by measurement of the metabolic activity of liver metastases by FDG-PET and SUV measurements. Secondary endpoints Toxicity of neo-adjuvant treatment Complications of surgery