(IMC-C225 -- marketed under the name Erbitux
) is a chimeric monoclonal antibody
, an epidermal growth factor receptor
, given by intravenous injection
for treatment of metastatic colorectal cancer
and head and neck cancer. Cetuximab was discovered by ImClone Systems
and is distributed in North America by ImClone and Bristol-Myers Squibb
, while in the rest of the world distribution is by Merck KGaA
Cetuximab costs $30,000 for eight weeks of treatment per patient.
Mode of action
Cetuximab is believed to operate by binding to the extracellular domain of the EGFR
of all cells that express EGFR, preventing ligand binding and activation of the receptor. This blocks the downstream signaling of EGFR resulting in impaired cell growth and proliferation. Cetuximab has also been shown to mediate antibody dependent cellular cytotoxicity (ADCC
Cetuximab is used in metastatic colon cancer
and is given concurrently with the chemotherapy drug irinotecan
(Camptosar), a form of chemotherapy
that blocks the effect of DNA topoisomerase I
, resulting in fatal damage to the DNA of affected cells. While there remains some scientific controversy on this, assessment for EGFR expression is required for use in Colorectal Cancer, but not in Head & Neck Cancer. It is best to refer to updated Prescription Information.
Cetuximab was approved by the FDA
in March 2006 for use in combination with radiation therapy
for treating squamous cell carcinoma
of the head and neck (SCCHN) or as a single agent in patients who have had prior platinum-based therapy.
One of the side effects of Cetuximab therapy is the incidence of, possibly severe, acne-like rash.
ImClone insider trading scandal
The initial failure of ImClone Systems to prepare an acceptable FDA filing led to the infamous Martha Stewart insider trading scandal when ImClone's CEO sold ImClone shares and this information was leaked to Stewart before the FDA announced its refusal to approve the drug for public use. Martha Stewart, Samuel D. Waksal (the founder and former CEO of ImClone), and their broker were indicted, and Stewart and Waksal were sentenced to prison. ImClone shares dropped sharply in the aftermath of the insider trading scandal.
A new clinical trial and FDA filing prepared by Imclone's partner Merck KGaA ("German Merck," not to be confused with the US company of similar name) resulted in an FDA approval of the drug in 2004 for use in the treatment of colon cancer.
Research studies have indicated that detection of KRAS
gene mutations helps physicians identify patients that are unlikely to respond to treatment with targeted EGFR inhibitors
, including cetuximab and panitumumab. Accordingly, genetic testing to confirm the absence of KRAS mutations is likely to become more common before starting treatment with EGFR inhibitors