Targeted therapies for patients with advanced colorectal cancer: focus on cetuximab

Colorectal cancer (CRC) is the fourth most common cancer in men and the third in women worldwide. Combinations of 5-fluorouracil (5-FU)/folinic acid (FA) with irinotecan or oxaliplatin form the standard treatment approaches for metastatic disease. The introduction of targeted agents has presented the opportunity to improve on the efficacy of current treatments without exacerbating the associated toxicity. Cetuximab (Erbitux (R)) is an IgG1 monoclonal antibody (MAb) that specifically targets the epidermal growth factor receptor (EGFR) with high affinity and competitively inhibits endogenous ligand binding. Cetuximab has shown good efficacy in combination with irinotecan in CRC that had previously progressed on irinotecan-based therapy. Cetuximab plus irinotecan and various schedules of 5-FU/FA have shown efficacy in a first-line setting. The activity of cetuximab and oxaliplatin-based regimens is being investigated in both first- and subsequent-line settings. Cetuximab is well tolerated and does not increase the side effect profile of agents it is combined with. Other EGFR inhibitors, including the tyrosine kinase inhibitors, gefitinib and erlotinib, and the MAbs, panitumumab and matuzumab, are also being investigated in a number of solid tumors. The vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, although apparently inactive as a single agent, has demonstrated survival benefits when combined with bolus 5-FU/FA and irinotecan in a first-line setting and with 5-FU/FA and oxaliplatin in the second-line treatment of metastatic CRC. In this paper we discuss the use of targeted therapies in the treatment of metastatic CRC, with a focus on cetuximab.