Novel chemotherapeutic and targeted agents in metastatic colorectal cancer: the time has arrived.

Colorectal cancer is a common disease with a high rate of mortality and very well-understood genetics. Primary therapy still consists of relatively non-specific treatments: surgery, radiotherapy and chemotherapy. In this article, recent data in the now fast-moving field of treatment of unresectable metastatic colorectal cancer are reviewed, beginning with new developments in conventional cytotoxic therapies. A number of new cytotoxic agents appear to have at least some activity in this disease, including classes of drugs that have been effective to date. The very rapidly growing area of targeted therapy will also be expanded upon. This year, for the first time, there has been a targeted therapy shown convincingly to prolong survival for patients with unresectable metastatic colorectal cancer in a well-performed Phase III trial. This agent is bevacizumab, a humanised monoclonal antibody targeting the circulating proangiogenic growth factor vascular endothelial growth factor. Results with bevacizumab should lead to rapid expansion of the number of strategies targeting tumour neovasculature. Additionally, an antibody against the epidermal growth factor, cetuximab, has been shown to have both single-agent activity and the potential ability to partially reverse resistance to a chemotherapy drug. These advancements, as well as data on other novel treatment agents that have been studied specifically in patients with colorectal neoplasms, are discussed in detail.