title: A phase II open-label multicenter study of gefitinib in combination with irradiation followed by chemotherapy in patients with inoperable stage III non-small cell lung cancer.
abstract: BACKGROUND
  Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer.
  
  
  METHODS
  This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy (66 Gy in 6.5 weeks, 2 Gy/day, 5 fractions/week) followed by consolidation chemotherapy (IV cisplatin and vinorelbine) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status.
  
  
  RESULTS
  Due to a low accrual rate in this study, the sample size (n = 50) was not reached. Sixteen patients were included in four centers, 50% had adenocarcinoma and 75% were male. Genomic alterations (7 patients studied) retrieved TP53 mutation in 2 patients and no EGFR mutation. Four weeks after radiotherapy, 3 patients (19%) had a partial response, 6 (38%) had a stable disease, and 7 had a progression (44%). Median overall survival was 11 months and median progression-free survival was 5 months. At the time of the last contact, 5 patients (31%) were still alive. Main toxicities were gastrointestinal (81%), cutaneous (81%), general (56%), and respiratory (50%). There were 12>G3 adverse events in 7 (47%) patients, and there was one toxic-death during the concomitant period due to an interstitial pneumonitis. There were two possible adverse events-related deaths during the chemotherapy period (pulmonary embolism (n = 1) and sudden death after the administration of the 3rd course of chemotherapy (n = 1)).
  
  
  CONCLUSIONS
  The benefit of Gefitinib-RT could not be confirmed due to premature trial discontinuation. Further evaluation is required, especially in patients with EGFR mutated NSCLC.
authors.affiliation: Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, Institut Thoracique d'Oncologie (IOT), Villejuif, France.|INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, Villejuif, France.|Univ Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Levy
authors.affiliation: Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Bardet
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Department of Biostatistics and Epidemiology, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lacas
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Department of Biostatistics and Epidemiology, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.affiliation: Department of Medical Biology and Pathology, Translational Research Laboratory and Biobank (UMS3655 CNRS / US23 INSERM), INSERM Unit U981, Villejuif, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Adam
authors.affiliation: Department of Medical Biology and Pathology, Translational Research Laboratory and Biobank (UMS3655 CNRS / US23 INSERM), INSERM Unit U981, Villejuif, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: Department of Radiation Oncology, University Hospital Grenoble, Grenoble, France.|Department of Radiation Oncology, St Grégoire Hospital, St Grégoire, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Artignan
authors.affiliation: Department of Radiation Oncology, Centre Jean Perrin, Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Verrelle
authors.affiliation: Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, Institut Thoracique d'Oncologie (IOT), Villejuif, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Le Péchoux
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D011799:Quinazolines; D000077156:Gefitinib
keywords: iressa; lung cancer; phase II trial; thoracic radiotherapy