Cetuximab
From Wikipedia, the free encyclopedia
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Cetuximab
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| Source | chimeric |
| Target | EGF receptor |
| Identifiers | |
| CAS number | |
| ATC code | L01 |
| DrugBank | |
| Chemical data | |
| Formula | C6484H10042N1732O2023S36 |
| Mol. mass | 145781.6 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | 114 hrs |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Cetuximab (marketed under the name Erbitux) is a chimeric monoclonal antibody, an EGFR inhibitor, 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 faces stiff competition from bevacizumab (Avastin), made by Genentech, and potential competition from panitumumab, currently under development by Amgen and Abgenix.
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[edit] Mode of action
Cetuximab is believed to operate by binding to the extracellular domain of the epidermal growth factor receptor (EGFR) of cancer cells, preventing ligand binding and activation of the receptor. This blocks the downstream signaling of EGFR resulting in impaired cell growth and proliferation.
[edit] Clinical uses
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 is a medical laboratory test to detect if a cancer tumor overexpresses epidermal growth factor receptor(EGFR) on its cells surface, this overexpression has recently been shown to not have any bearing on whether a patient will respond to Cetuximab or not[citation needed]. Whether this is because the current tests are just not sensitive enough to detect EGFR overexpression or because EGFR overexpression is not linked to the drugs effectiveness has not been established. Cetuximab was approved by the FDA in March 2006 after the publication of research performed by Dr J. Bonner [1] 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 sever, acne like rash.
[edit] 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 colon cancer.
Erbitux® is one of the most expensive drugs available, costing over $17,000 per month for the average dose.[citation needed]
[edit] External links
- FDA Erbitux (cetuximab) Information Page
- Erbitux site from Bristol-Myers Squibb, ImClone Systems, and Merck KGaA
- Anti EGFreceptor monoclonals and small molecules on the web
