Gefitinib


Gefitinibb Treatment
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Gefitinib

Gefitinib

Gefitinib is a cancer treatment marketed under the brand name Iressa. It is not a chemotherapeutic in the traditional sense, since it does not cause the destruction of tumor cells. Instead, gefitnib interferes with the growth and spread of new cancer cells. In this respect, gefitnib is an antitumor medication rather than a cytotoxic (cell killing) drug. It is part of the class of cancer drugs known as tyrosine kinase inhibitors.

Gefitnib inhibits the phosphorylation of several tyrosine kinases inside of cells. One tyrosine kinase that gefitnib inhibits that is believed to play a role in its antitumor effect is the tyrosine kinase associated with the epidermal growth factor receptor. Epidermal growth factor receptor is a receptor that is found on both normal and cancer cells, but its presence on cancer cells is believed to explain at least some of gefitnib's antitumor effect.

Astra Zeneca received FDA approval for gefitnib (Iressa) in May 2003. The drug's original indication was for the treatment of advanced or malignant non-small cell lung cancer in patients that failed traditional treatment, specifically platinum and docetaxel chemotherapies. Gefitnib was approved by the FDA under accelerated approval regulations. Large clinical trials with the drug showed that it only benefitted about 10% of the patients that used the drug.

As a result, the FDA approved updated labeling and prescribing information in June 2005 that reflects a restricted approval of the drug. The current FDA approval is limited to patients that have been successfully treated or are currently treated with the drug. The approval is limited to the treatment of non-small cell lung cancer that has not responded to traditional treatment. In these patients it can be used as monotherapy, meaning the sole cancer treatment.

Theoretically, a tyrosine kinase inhibitor like gefitnib could be used in other cancers besides non-small cell lung cancer. Since it blocks the epidermal growth factor receptor tyrosine kinase, any cancer cell that expresses this protein in large amounts could be affected by the drug. The only large scale trial registered with the National Institutes of Health (NIH) to investigate the use of gefitnib in other types of cancer is one that examines the effect of the drug on recurrent glioblastoma, a type of brain tumor.

The fact that gefitnib is only effective in 10% of patients treated with the drug may be due to a particular mutation in the epidermal growth factor receptor. A group of researchers in Japan found that patients with this mutation enjoyed longer progression-free survival than those without the mutation.1 It is estimated that the 10% effect seen in large trials is approximately the percentage of patients that naturally have this mutation. Therefore, companies have developed or are developing a laboratory test to determine if a given patient has the proper mutation in this gene. A positive result on this test should predict whether gefitnib will be effective in that patient. Currently Genzyme Genetics and Biodesix offer testing for the mutation of the epidermal growth factor receptor-tyrosine kinase gene at a cost of about $1,000.

Perhaps surprisingly, the effect of gefitnib did not correlate to the amount of epidermal growth factor receptor on cancer cells. One might expect this to be the case given its proposed mechanism of action. Another drug called erlotinib (Tarceva) works by a similar mechanism as gefitnib and is approved in the same patient population. Erlotinib was approved on the basis of survival data and its effect does correlate with the amount of receptor present. In other words, patients that expressed a large amount of epidermal growth factor receptor had better results with erlotinib than those patients with lower amounts of the receptor protein.

Compared to cytotoxic anticancer drugs, gefitnib has a relatively tolerable side effect profile. Its only serious documented side effect is that it can cause damage to lungs in the form of interstitial lung disease. This occurs in about 1% of patients treated with gefitnib and the lung condition has been directly fatal in a third of patients that develop the side effect.

 

Gefitinibb Treatment
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