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Lung cancer blog: Why some lung cancers stop responding to tarceva

Back to Lung cancer blog Lung cancer main Non small cell  

Sep 15, 2005

Why some lung cancers stop responding to tarceva

Why some lung cancers stop responding to tarcevaScientists have recently found an explanation for why some lung cancers stop responding to the drugs erlotinib (Tarceva) and gefitinib (Iressa). Gefitinib and erlotinib are so-called targeted therapies. The two drugs are effective in about 10 percent of US patients with non-small cell lung cancer (NSCLC). Previous work have showed that these two drugs work specifically in patients whose cancers contain mutations in a gene that encodes the epidermal growth factor receptor (EGFR). Lung cancer patients with these mutations are often people who have never smoked. This discovery may lead to the development of new therapies to use when these agents stop working.

"Even though these targeted therapies are initially effective in this subset of patients, the drugs eventually stop working, and the tumors begin to grow again. We call this acquired or secondary resistance," said Vincent A. Miller, MD, a thoracic oncologist at MSKCC and one of the study's two lead authors. "This is different from primary resistance, which means that the drugs never work at all," Dr. Miller said.

The study involved six patients who had received treatment with gefitinib or erlotinib and who later developed acquired resistance. Scientists studied samples taken from the patients' tumors at different times before and during treatment. All of the tumors had the kinds of mutations in the EGFR gene that were previously associated with responsiveness to these drugs. But, in three of the six patients, they found that tumors that grew despite continued therapy had an additional mutation in the EGFR gene, strongly implying that the second mutation was the cause of drug resistance. Further biochemical studies showed that this second EGFR mutation, which was the same in all three tumors, could confer resistance to the EGFR mutants normally sensitive to these drugs.

Please note that Gefitinib (Iressa) is no longer promoted in the U.S. Market because it did not demonstrate a survival advantage in a large randomized clinical trial. Gefitinib is still available through special programs.


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Lung cancer blog: Why some lung cancers stop responding to tarceva

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