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A Journal on Internal Medicine

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Minerva Medica 2004 June;95(3):233-42

language: Italian

Preclinical and clinical results with the epidermal growth factor receptor inhibitor Gefitinib (ZD1839,Iressa)

Di Cosimo S., Ferretti G., Milella M., Martinelli E., Alimonti A., Papaldo P., Carlini P., Fabi A., Matar P., Cognetti F.


Since epidermal growth factor receptor (EGFR) is involved in tumor proliferation and angiogenesis, and in the mechanisms of resistance to chemo- and hormono-therapy, it represents a unique promising target for anticancer treatment. Gefinitib (Iressa, ZD1839), an inhibitor of the EGFR tyrosine kinase activity able to bind the intracellular domain of the receptor, is at present in clinical development. In preclinical models Gefitinib induced a dose-dependent response rate in tumor xenografts obtained from different human cancer cells lines. The expression of EGFR in the prior tumor did not appear to be a predictive marker for Gefitinib sensitivity. Furthermore, long-term drug use was well tolerated in mice without inducing resistance. However, tumors started to grow again after treatment interruption. Laboratory findings and in vivo data have prompted the evaluation of Gefitinib administered as a single oral daily dose alone or in combination with conventional anticancer treatment.

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