First-line treatment in advanced colorectal cancer - New options in metastatic disease

The last ten years have seen tremendous progress in the treatment of colorectal carcinoma. With at least seven currently available therapies, the landscape of metastatic disease continues to evolve. This review discusses the development of first-line therapy in advanced colorectal cancer, from single agent to combination cytotoxic therapy with the addition of biologics. The trials pivotal in this evolution of care to a new standard will be discussed as well as the emerging role pharmacogenomics plays in treatment decisions. Since 2004, the standard of care has been combination therapy with infusional 5-fluorouracil and oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). To prolong overall survival, patients should be exposed to all three agents over the course of treatment. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, appears to modestly improve survival in both first- and second-line therapies when combined with FOLFOX or FOLFIRI. Epidermal growth factor receptor inhibitors, like cetuximab and panitumumab, likewise generated much excitement when first introduced. This enthusiasm was subsequently tempered by modest improvement in progression-free survival when combined with combination chemotherapy. Recent data, however, suggests that patients whose tumors have KRAS mutations do not benefit from epidermal growth factor receptor inhibition, and it is only patients with tumors that exhibit wild-type KRAS who should be considered for this therapy. It appears that patient selection is the key to further improving survival with currently available therapies.