Cetuximab
From Wikipedia, the free encyclopedia
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Cetuximab?
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| Therapeutic monoclonal antibody | |
| Source | chimeric |
| Target | EGF receptor |
| Identifiers | |
| CAS number | |
| ATC code | L01 |
| PubChem | ? |
| DrugBank | |
| Chemical data | |
| Formula | C6484H10042N1732O2023S36 |
| Mol. mass | 145781.6 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | 114 hrs |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
Cetuximab (marketed under the name Erbitux) is a chimeric monoclonal antibody, an epidermal growth factor receptor (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[citation needed] from panitumumab (Vectibix), from Amgen approved by the FDA in November 2006. One of the main differences is that Cetuximab is an IgG1 antibody, and Panitumumab an IgG2 one. Their properties are not absolutely identical.[1] Cetuximab costs $30,000 for eight weeks of treatment per patient.[2]
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[edit] Mode of action
Cetuximab is believed to operate by binding to the extracellular domain of the EGFR of all cells that express EGFR, which includes the subset "cancer cells", 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).
[edit] Clinical uses
[edit] Colorectal Cancer
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[3].
[edit] Head and neck cancer
Cetuximab was approved by the FDA in March 2006[4] 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.
[edit] ImClone insider trading scandal
- Further information: ImClone Systems#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.
[edit] References
- ^ IgG1_IgG2
- ^ Schrag, D (Jul 2004). "The price tag on progress – chemotherapy for colorectal cancer". New England Journal of Medicine 351 (4): 317-319. doi:.
- ^ http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%20from%20TB_PRODUCT_PPI%20where%20PPI_SEQ=106&key=PPI
- ^ Cetuximab Beneficial in Head and Neck Cancer - National Cancer Institute
[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
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