Cetuximab (Erbitux) is a chimeric IgG1k monoclonal antibody directed against the epidermal growth factor receptor (EGFR; also known as ErbB-1 and Her1). EGFR is present on normal epithelial tissues, as well as human cancers such as those of the head and neck, colon and rectum. Cetuximab competitively inhibits the binding of ligands (EGF, TGFa, amphiregulin and others) to EGFR, and thereby blocks its signaling cascade. This leads to inhibition of cell growth, induction of apoptosis, and decreased pro-inflammatory cytokine and vascular growth factor production. The K-Ras gene is downstream of EGFR in the signaling cascade. Patients with a mutated K-Ras gene therefore do not respond to cetuximab, such that the presence of such mututations needs to be excluded before treating with cetuximab. The drug is administered intravenously every two weeks. Cetuximab was approved in 2004 by the FDA for the treatment of metastatic carcinomas of the colon and rectum. For this indication, it improves overall progression-free survival and preserves the quality of life in patients who have not responded to chemotherapy. The use of cetuximab to treat head and neck cancer was approved in 2011. The FDA granted in 2012 approval to cetuximab for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) for treatment of patients with K-ras mutation-negative, EGFR-expressing metastatic colorectal cancer. Recently presented results from CAPRI-GOIM study demonstrated the efficacy of cetuximab plus FOLFOX chemotherapy as second-line treatment for patients withmetastatic colorectal cancer. The most serious adverse reactions observed in clinical trials of cetuximab, alone or in combination with irinotecan, were infusion reactions, dermatologic toxicity, interstitial lung disease, fever, sepsis, renal dysfunction, pulmonary embolism, dehydration, and diarrhea.