The role of gefitinib in lung cancer treatment.
Gefitinib (Iressa) is a novel targeted therapy that inhibits the tyrosine kinase activity of the epidermal growth factor receptor by competitively blocking the ATP binding site. In preclinical studies gefitinib has shown potent activity in a number of tumor models, including several lung cancer cell lines and xenografts. Two large randomized Phase II studies (IDEAL 1 and IDEAL 2) in pretreated non-small cell lung cancer reported a response rate approaching 20% in second-line patients and approximately 10% in those pretreated with two or more chemotherapy regimens. The median survival in these two studies approached 6-8 months. As a first-line therapy, gefitinib has been assessed in combination with two different chemotherapy regimens in two large randomized studies (INTACT 1 and INTACT 2). Both studies failed to show an improvement in survival on a total patient accrual of >1000 patients in each study. Other end points (e.g., time to progression and response rate) were also not improved by the addition of gefitinib. Additional studies are indicated to assess the possible role of gefitinib in the maintenance of patients who received chemotherapy or chemoradiotherapy. Studies investigating gefitinib as first-line monotherapy are also required.
Giaccone
Giuseppe
G
Division of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. g.giacconne@vumc.nl
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
D000970:Antineoplastic Agents; D011799:Quinazolines; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib