Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer.
BACKGROUND
Cetuximab is a recombinant human/mouse chimeric epidermal growth factor receptor (EGFR) monoclonal antibody. It was approved by the US Food and Drug Administration in February 2004 to be used in combination with irinotecan for the treatment of EGFR-expressing, metastatic colorectal cancer in patients who had failed to improve with irinotecan-based chemotherapy. Cetuximab was also approved for administration as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy.


OBJECTIVE
This article reviews the role of cetuximab, an EGFR monoclonal antibody, in the treatment of colorectal cancer.


METHODS
A MEDLINE search was conducted of articles published from 1976 to the present using the terms cetuximab, C225, IMC-C225, colon cancer, colorectal cancer, monoclonal therapy, and target therapy. Abstracts presented at the American Society of Clinical Oncology annual meetings from 2000 to 2004 and the 2004 Gastrointestinal Cancers Symposium were reviewed and included as applicable.


RESULTS
In a Phase III trial, cetuximab was administered to 329 patients with colorectal cancer who were irinotecan refractory and/or had failed to respond to oxaliplatin treatment. Partial response was achieved in 10.8% of patients who received cetuximab monotherapy and 22.9% of patients who received cetuximab plus irinotecan therapy (P = 0.007). The overall response rate in 2 Phase II trials using the conventional dosing regimen of cetuximab to treat EGFR-expressing, metastatic colorectal cancer that was refractory to irinotecan therapy ranged from 9% to 12%. The drug was well tolerated with proper administration precautions. The most common adverse events reported included acnelike rash and hypersensitivity reaction. The positive correlation of the incidence of skin reactions to response rates and median survival is one aspect that warrants further investigation in terms of its use as a response predictor. Unfortunately, the role of immunohistochemistry for EGFR expression continues to be a poor predictor of patients who may benefit from cetuximab. Clinical studies are ongoing of cetuximab in combination with radiation therapy and/or platinum in patients with squamous cell head and neck cancer, as well as cetuximab in combination with various antineoplastic agents in the treatment of non-small cell lung cancer and pancreatic cancer.


CONCLUSIONS
Cetuximab has shown considerable activity-both as monotherapy and in combination with chemotherapy-in the treatment of metastatic colorectal cancer that is resistant to chemotherapy. The future of cetuximab lies in its use in combination with antineoplastic agents and/or radiation therapy in the treatment of colorectal cancer, head and neck cancer, non-small cell lung cancer, and pancreatic cancer. The lack of a predictive marker that would allow clinicians to select patients who are most likely to benefit from cetuximab therapy, especially taking into consideration the high costs of this medication, remains a challenge.
Wong
Siu-Fun
SF
Western University College of Pharmacy, Pomona, CA 91766, USA. siuwong@westernu.edu
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab