title: Sorafenib in combination with erlotinib or with gemcitabine in elderly patients with advanced non-small-cell lung cancer: a randomized phase II study.
abstract: BACKGROUND
  Sorafenib is a small-molecule multitargeted kinase inhibitor that blocks the activation of C-RAF, B-RAF, c-KIT, FLT-3, RET, vascular endothelial growth factor receptor 2 (VEGFR-2), VEGFR-3 and platelet-derived growth factor receptor β. The aim of this multicenter, randomized phase II study was to evaluate clinical activity and safety of sorafenib in combination with erlotinib or gemcitabine in unselected untreated elderly patients with non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  The trial was designed to select the most promising sorafenib-containing combination in previously untreated elderly (≥70 years) stage IIIB or IV NSCLC patients, with performance status of zero to two. Patients were randomly assigned to one of the following combinations: gemcitabine, 1200 mg/m(2) days 1 and 8, every 21 days, for a maximum of six cycles, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 1); or erlotinib, 150 mg/day, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 2). A selection design was applied with 1-year survival rate as the primary end point of the study, requiring 58 patients.
  
  
  RESULTS
  Sixty patients were randomly allocated to the study (31 patients in arm 1 and 29 patients in arm 2). After a median follow-up of 15 months, 10 patients [32%, 95% confidence interval (CI) 16% to 49%] in arm 1 and 13 patients (45%, 95% CI 27% to 63%) in arm 2 were alive at 1 year. Median overall survival was 6.6 and 12.6 months in arm 1 and arm 2, respectively. Observed toxic effects were consistent with the expected drug profiles.
  
  
  CONCLUSIONS
  The combination of erlotinib and sorafenib was feasible in elderly patients with advanced NSCLC and was associated with a higher 1-year survival rate than the other arm. According to the selection design, this combination warrants further investigation in phase III trials.
authors.affiliation: Division of Medical Oncology, S.G. Moscati Hospital, Avellino.
authors.forename: C
authors.initials: C
authors.lastname: Gridelli
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, Naples.
authors.forename: F
authors.initials: F
authors.lastname: Morgillo
authors.affiliation: Division of Medical Oncology II, Istituto Oncologico Veneto, Padua.
authors.forename: A
authors.initials: A
authors.lastname: Favaretto
authors.affiliation: Thoracic-Oncology Unit 1st, Lung Diseases Department, San Camillo Hospital, Rome.
authors.forename: F
authors.initials: F
authors.lastname: de Marinis
authors.affiliation: Pulmonary Unit, University Hospital of Pisa, Pisa.
authors.forename: A
authors.initials: A
authors.lastname: Chella
authors.affiliation: The Falck Division of Medical Oncology, Ospedale Niguarda Ca' Granda, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Cerea
authors.affiliation: Medical Oncology Unit, S. Croce Hospital, Fano.
authors.forename: R
authors.initials: R
authors.lastname: Mattioli
authors.affiliation: Medical Oncology Unit, Department of Molecular and Clinical Endocrinology, University of Naples "Federico II".
authors.forename: G
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Division of Medical Oncology, S.G. Moscati Hospital, Avellino.
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, Naples.
authors.forename: M
authors.initials: M
authors.lastname: Fasano
authors.affiliation: Division of Medical Oncology II, Istituto Oncologico Veneto, Padua.
authors.forename: G
authors.initials: G
authors.lastname: Pasello
authors.affiliation: Thoracic-Oncology Unit 1st, Lung Diseases Department, San Camillo Hospital, Rome.
authors.forename: S
authors.initials: S
authors.lastname: Ricciardi
authors.affiliation: Division of Medical Oncology, S.G. Moscati Hospital, Avellino.
authors.forename: P
authors.initials: P
authors.lastname: Maione
authors.affiliation: Clinical Trials Unit, National Cancer Institute, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, Naples. Electronic address: fortunato.ciardiello@unina2.it.
authors.forename: F
authors.initials: F
authors.lastname: Ciardiello
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D011799:Quinazolines; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine