Iressa or gefitinib targets epidermal growth factor receptor and disrupts its intracellular behavior. This was hoped to have significant anti-cancer effects.
Unfortunately, it seems increasingly that the clinical benefit of Iressa is limited. Although it showed some benefit in treating certain types of cancer in certain populations, especially in people of Asian descent, as of writing, it has not been judged a success.
The epidermal growth factor (EGF) family was discovered in the 1960s and have increasingly been shown to be involved in tumor development. Cells that express excessive receptors for EGF may become carcinogenic, and activation by binding can stimulate pathways such as Ras/raf, JAK-STAT and others.
That leads to increased proliferation, motility and invasion.
As such, we developed drugs like Iressa or Gefatinib that specifically target the EGF receptors. Unfortunately, results have not been especially positive for that class. Even when we test the tumor and see that it is positive for excessive EGF receptors, that is not a clear indication that response to treatment will be good.
There may be other mutations in cancerous cells that develop resistance to anti-EGF receptor treatment. And if there aren’t any initially, resistance may develop upon treatment.
As of July 2008, almost 300,000 patients with non-small cell lung cancer have been treated with Gefatinib. Of those, the most clinical benefit was seen in Asian patients. Smaller studies like IDAEL1 showed no benefit in the population as a whole, but an almost 50% increase in survival time in Japanese patients. Additionally, another study showed insignificant benefit overall, but perhaps some benefit in patients who had never smoked in their lives.
Other studies have shown similar, mixed results. Even in the populations which may benefit most from treatment, it seems like Iressa or Gefatinib may not be an ideal treatment, even as a secondary option, as there are other options like erlotinib which may have superior efficacy.
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