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World J Gastroenterol. Apr 21, 2014; 20(15): 4208-4219
Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4208
Role of cetuximab in first-line treatment of metastatic colorectal cancer
Miguel Jhonatan Sotelo, Beatriz García-Paredes, Carlos Aguado, Javier Sastre, Eduardo Díaz-Rubio
Miguel Jhonatan Sotelo, Beatriz García-Paredes, Carlos Aguado, Javier Sastre, Eduardo Díaz-Rubio, Center affiliate to the “Red Temática de Investigación Cooperativa (RD12/0036/006)”, Instituto Carlos III, Spanish Ministry of Economy and Competitivity. Oncology Department, Hospital Clínico San Carlos, 28040 Madrid, Spain
Author contributions: Sotelo MJ, García-Paredes B, Aguado C, Sastre J and Díaz-Rubio E designed, wrote and approved the final version of the manuscript.
Correspondence to: Eduardo Díaz-Rubio, MD, PhD, Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Oncology Department, Hospital Clínico San Carlos. Prof. Martín Lagos, s/n, 28040 Madrid, Spain. ediazrubio.hcsc@salud.madrid.org
Telephone: +34-91-3303546 Fax: + 34-91-3303546
Received: September 20, 2013
Revised: January 1, 2014
Accepted: February 17, 2014
Published online: April 21, 2014
Processing time: 211 Days and 12.3 Hours
Abstract

The treatment of metastatic colorectal cancer (mCRC) has evolved considerably in the last decade, currently allowing most mCRC patients to live more than two years. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor play an important role in the current treatment of these patients. However, only antibodies directed against EGFR have a predictive marker of response, which is the mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Cetuximab has been shown to be effective in patients with KRAS wild-type mCRC. The CRYSTAL study showed that adding cetuximab to FOLFIRI (regimen of irinotecan, infusional fluorouracil and leucovorin) significantly improved results in the first-line treatment of KRAS wild-type mCRC. However, results that evaluate the efficacy of cetuximab in combination with oxaliplatin-based chemotherapy in this setting are contradictory. On the other hand, recent advances in the management of colorectal liver metastases have improved survival in these patients. Adding cetuximab to standard chemotherapy increases the response rate in patients with wild-type KRAS and can thus increase the resectability rate of liver metastases in this group of patients. In this paper we review the different studies assessing the efficacy of cetuximab in the first-line treatment of mCRC.

Keywords: Cetuximab; First-line; Metastatic colorectal cancer; Colorectal liver metastases; Elderly patients

Core tip: This article contains updated data regarding biomarkers of response to epidermal growth factor receptor-targeted therapy and reviews the major studies that have evaluated the efficacy of cetuximab in the first-line treatment of metastatic colorectal cancer (mCRC). We have also compiled the most important data supporting the use of cetuximab in the neoadjuvant treatment of colorectal liver metastases. Finally, we review the current evidence regarding the efficacy and safety of cetuximab in the treatment of elderly patients with mCRC.