Adjuvant chemotherapy and targeted agents After resection of liver metastases, up to 70% of patients may develop recurrence of disease either in the liver or in extra-hepatic locations, thus providing rationale for postoperative or adjuvant chemotherapy (68). However, data

for systemic therapies in this setting is severely lacking. Inhibitors,research,lifescience,medical If data from patients with stage III disease were extrapolated to stage IV patients, then chemotherapy regimens would be recommended since recurrence was lower and OS was higher with adjuvant chemotherapy. However, neither bevacizumab nor cetuximab in the adjuvant setting provided survival benefits when combined with chemotherapy in stage III trials (69,70). Regardless, it may not be reasonable to compare complete resection of disease in stage III patients who have locoregional disease with stage IV patients Inhibitors,research,lifescience,medical who have distant metastatic disease. Currently, no Level 1 recommendation based on a randomized trial can be made regarding adjuvant targeted therapy after resection of CRLM. Nevertheless, most patients will receive some form of adjuvant therapy

given the improved outcomes with standard and targeted therapies in patients with mCRC. Management of the primary tumor The management of the primary tumor is a Inhibitors,research,lifescience,medical topic of controversy in patients with unresectable mCRC. The current strategy is to leave the primary cancer in place unless there are complications that include bleeding, obstruction, or perforation. Inhibitors,research,lifescience,medical This strategy is based upon the observation that patients receiving chemotherapy or targeted agents do not have increased rates of complications or emergent resections (NSABP C-10) (71). However, a recent retrospective analysis suggested a potential survival benefit with resection of the primary tumor when mCRC was unresectable (72). More work is needed

to clarify the most appropriate management of the primary tumor in patients with unresectable mCRC. The future is now: novel targeted agents Ziv-aflibercept and regorafenib are two newly approved targeted agents for mCRC. Ziv-aflibercept is a Inhibitors,research,lifescience,medical soluble recombinant protein that acts as a “trap” for multiple angiogenic factors (73). This protein interferes with angiogenesis by binding to VEGF-A, VEGF-B, and placental growth factor (PlGF), GPX6 thus “trapping” these growth factors and Selleckchem RO4929097 preventing binding to and activation of VEGF receptors, thereby interfering with angiogenesis. In the phase III randomized, double-blind, multi-national VELOUR trial, patients with mCRC previously treated with oxaliplatin were randomized to receive ziv-aflibercept or placebo every two weeks in combination with FOLFIRI (33) with the primary endpoint of OS. At a median follow-up time of 22.3 months, patients receiving ziv-aflibercept had significant increases in both OS (median, 13.5 vs. 12.1 mos, respectively) and ORR (19.8% vs. 11.