title: Gefitinib (ZD1839, Iressa) in non-small-cell lung cancer: a review of clinical trials from a daily practice perspective.
abstract: Gefitinib (ZD1839) is the most widely studied targeting agent in the area of non-small-cell lung cancer (NSCLC). Gefitinib is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor. In order to assess the role of gefitinib in the management of NSCLC patients, we systematically reviewed published clinical trials from a daily practice perspective. A systematic research was made in the international medical literature. Gefitinib demonstrated a good tolerance and an encouraging efficacy in pretreated NSCLC patients in preclinical studies. These results were then confirmed in two phase II trials (IDEAL 1 and 2) involving more than 400 patients mostly pretreated with a platinum-containing regimen and docetaxel. All these results were reinforced by those of retrospective studies on patients enrolled in a compassionate use programme. Thus, two phase III trials in chemo-naive patients were initiated (INTACT 1 and 2). Unfortunately, the use of gefitinib with standard combination chemotherapy provided no survival benefit nor response rate or progression-free survival improvement over placebo. Furthermore, we also reviewed the results of studies interested in the characterization of predictive clinical or biological markers for response to gefitinib and discussed the results obtained with other EGFR inhibitors. The efficacy of gefitinib in the first-line setting of each stage of NSCLC has to be further studied through clinical trials. Furthermore, translational studies characterizing the molecular features involved in the response to anti-EGFR-targeted therapies are needed.
authors.affiliation: Faculty of Medicine, University of Méditerranée (Aix-Marseille II), Assistance Publique Hôpitaux de Marseille, Thoracic Oncolfaogy Unit, Respiratory Disease Federation, Hôpital Sainte-Marguerite, Marseille, France. fabrice.barlesi@mail.ap-hm.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlési
authors.forename: Cécile
authors.initials: C
authors.lastname: Tchouhadjian
authors.forename: Christophe
authors.initials: C
authors.lastname: Doddoli
authors.forename: Patrick
authors.initials: P
authors.lastname: Villani
authors.forename: Laurent
authors.initials: L
authors.lastname: Greillier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kleisbauer
authors.forename: Pascal
authors.initials: P
authors.lastname: Thomas
authors.forename: Philippe
authors.initials: P
authors.lastname: Astoul
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D016208:Databases, Factual; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib