Multiagent Regimens for Metastatic Colorectal Cancer: If Some Is Good, More Must Be Better

Extract

The management of patients with metastatic colorectal cancer has undergone substantial evolution over the past two decades. The advent of several new classes of therapeutics that have been approved for use in patients with colorectal cancer since the mid-1990s has resulted in tangible clinical benefit, with median survival currently expected to be in excess of 20 months ( 1–3 ). In an era not so long ago, 5-fluorouracil was the sole agent with generally recognized benefit in managing patients with colorectal cancer. The use of this agent was associated with a median survival of less than 1 year. Thus, recent advances have been substantial; however, it is humbling to realize that we still have considerable room for improvement in our therapeutic armamentarium. In addition to the development of new cytotoxic agents including oxaliplatin and irinotecan along with the antibody inhibitors of vascular endothelial growth factor and the epidermal growth factor receptor, we have learned that patients with metastatic colorectal cancer should not all be treated similarly nor should the goals of therapy be singular, namely palliation, as it was in a bygone era. We have also learned that the approximately 40% of patients whose tumors contain a mutation in the KRAS oncogene will not derive benefit from the use of antibody therapy directed against epidermal growth factor receptor ( 4 ).