Cetuximab

• CAS Number: 205923-56-4

Cetuximab (trade name: Erbitux ®, ImClone Systems, Bristol -Myers Squibb and Merck KGaA), is a therapeutic chimeric monoclonal antibody IgG1 against the epidermal growth factor receptor ( EGFR), which is used in oncology (cancer medicine) for cancer immunotherapy.

Mechanism of action

The antibody is directed against a tumor antigen, which is found in the membranes of human body cells. This enzyme, a receptor tyrosine kinase called EGFR ( epidermal growth factor receptor to German: Epidermal growth factor receptor ) receives chemical signals called growth factors, which are located in the tissue fluid, and then stimulates the cell metabolism. Cancer cells often have a lot of EGFR molecules in their cell membranes; in colorectal cancer EGFR is overexpressed in 80 % of the cells, that is much more often than in normal tissue cells. Cetuximab binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal -transduction pathway, which both the invasion of normal tissues by tumor cells and the spread of tumors to new sites (metastasis) can be reduced.

In addition, cetuximab appears to be the ability of tumor cells to inhibit, to repair damage caused by chemotherapy and radiotherapy. In addition is believed that it reduces the formation of new blood vessels in tumors, tumor growth counteracts.

After a series of successful clinical trials of cetuximab in 2003 in the United States was in 2004 in the European Community in 2008 and approved in Japan for treatment of colon cancer, as a means in cases where irinotecan cytostatic chemotherapy has failed.

Compared with cytostatics cetuximab side effects. The most commonly reported side effect with Erbitux is an acne-like rash, which in turn seems to be correlated with a good response to therapy. About 5 percent of patients may experience hypersensitivity reactions with Erbitux under treatment; about half of these reactions are severe.

A 2010 study published on Erbitux from Norway focuses on the benefits again in question. Thus was seen in 566 patients studied who were treated with Erbitux and a triple chemotherapy, no evidence of a prolongation of survival time.

Development and sales

The development of the drug goes on the scientific work of Joseph Schlessinger, Michael Sela, and other scientists at the Weizmann Institute of Science back. A short time later, cetuximab was patented by the New York biotech company ImClone Systems, which a patent dispute with the Weizmann Institute belonging Yeda Research and Development Company Ltd.. moved to itself, which Yeda largely decided for themselves. In the U.S. and Canada will cetuximab from Bristol -Myers Squibb sold outside of the USA from the Darmstadt pharmaceutical company Merck KGaA under license. For Japan, the three companies share the distribution rights. 2002, the approval of Erbitux had been denied by the U.S. Food and Drug Administration in the first attempt, surprisingly, which led to a sharp fall of ImClone stock. According to press reports, the application documents were incomplete. As the founder of ImClone, the brothers Samuel and Harlan Waksal, its shares were sold shortly before the crash, they came temporarily under the suspicion of the stock market manipulation. On 12 June 2002, Sam Waksal, former CEO of ImClone, was arrested on suspicion of insider trading. On 10 June 2003 he was sentenced to a term of imprisonment of 7 years and 3 months. A friend of his, Martha Stewart was convicted in this context, to six months ' imprisonment. 2008 ImClone was acquired by Eli Lilly. A 14-day cycle of therapy with cetuximab costs about 5000 euros, are common in colorectal cancer therapy twelve cycles.

Indications or approval

• For use in combination with irinotecan in patients with EGFR-expressing metastatic colorectal cancer who no longer respond to a prior irinotecan therapy, admission in 74 countries, including China, European Union, Liechtenstein, Switzerland and the United States is available. (As of September 2008 ) In the European Union there is the further restriction that may have to be treated tumors not a mutated KRAS gene. (April 2010 )

The approval for first-line treatment of advanced or metastatic non- small cell lung cancer has been requested by the manufacturing company on 11 September 2008. Basis of the application were the data of the so-called FLEX - study, in which an addition of cetuximab to platinum-based standard therapy, the median overall survival of the patients had improved by about one month.