Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract

Cetuximab is a recently approved monoclonal antibody that targets the epidermal growth factor receptor, a receptor tyrosine kinase involved in the development and progression of colorectal cancer (CRC) and other solid tumors. Cetuximab, as a single agent or in combination with chemotherapy, has demonstrated significant clinical efficacy against CRC. Combinations of cetuximab with chemotherapy have proven to be well tolerated, with minimal overlap of toxicities between agents; and the anticancer synergy between cetuximab and traditional chemotherapy agents has made cetuximab a vital treatment for patients who are no longer responsive to chemotherapy alone. The U. S. Food and Drug Administration approved cetuximab in combination with irinotecan for the treatment of irinotecan-refractory metastatic CRC or as monotherapy for treating patients intolerant to irinotecan. Combination chemotherapies involving cetuximab as well as combinations involving cetuximab and other targeted agents, such as bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, constitute powerful new treatment options for the management of CRC. This review discusses recent clinical studies that have further defined this synergy, focusing primarily on tumors of the gastrointestinal tract.