Clinical pharmacology and determinates of response to gefitinib in non-small cell lung cancer

Objective. Provide a review and update of gefitinib (Iressa®), including recent data on mutations in the epidermal growth factor receptor (EGFR) and possible implications in non-small cell lung cancer patients. Data sources. Primary literature and review articles were researched using Pub-Med. Articles through June 2004 were considered for preparation of the review. All clinical trials with published results and articles reporting EGFR mutations were considered for inclusion by the authors. Conclusions. Gefitinib is a novel EGFR tyrosine kinase inhibitor approved for treatment of chemoresistant NSCLC. Response rates of 10-19% have been observed in clinical trials with no improvement when combined with chemotherapy. Currently, gefitinib is used as a single agent for advanced NSCLC that is resistant to chemotherapy. Mutations in EGFR correlating with response to gefitinib have recently been described. Based on these early results, genetic testing of NSCLC patients upon diagnosis could predict response to gefitinib. Early treatment of NSCLC patients positive for EGFR mutations with gefitinib remains to be tested.