title: Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03).
abstract: OBJECTIVE
  Patients with brain metastases (BM) rarely survive longer than 6months and are commonly excluded from clinical trials. We explored two combined modality regimens with novel agents with single agent activity and radiosensitizing properties.
  
  
  METHODS
  In this randomised phase II trial patients with BM from NSCLC were randomly assigned to 30Gy WBRT with either concomitant gefitinib (GFT) 250mg/day continuously or temozolomide (TMZ) 75mg/m(2) for 21/28days. The primary end-point was overall survival, with quality of life and cognitive function as secondary end-points.
  
  
  RESULTS
  We enrolled 59 patients (GFT 16, TMZ 43), and 56 patients have died, mainly (80%) from disease progression. Four patients succumbed complications of the disease or corticosteroids (intestinal perforation (2), CNS haemorrhage and pulmonary emboli). Median overall survival in the gefitinib arm was 6.3months (95% CI 2.1-14.6), and 4.9months (95% CI 2.3-5.6) in TMZ treated patients. Fatigue was the main complaint.
  
  
  CONCLUSIONS
  No relevant toxicity with those therapeutic regimens was observed. Fatal outcome in three patients may have been related to corticosteroids. Cognitive function improved during treatment. However, median overall survival for all patients was only 4.9months (95% CI 2.3-5.7) and 1-year survival 25.4% (95% CI 15.4-37.0%).
authors.affiliation: Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland. GianfrancoAngelo.Pesce@eoc.ch
authors.forename: Gianfranco A
authors.initials: GA
authors.lastname: Pesce
authors.forename: Dirk
authors.initials: D
authors.lastname: Klingbiel
authors.forename: Karin
authors.initials: K
authors.lastname: Ribi
authors.forename: Abderahim
authors.initials: A
authors.lastname: Zouhair
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
authors.forename: Marc
authors.initials: M
authors.lastname: Schlaeppi
authors.forename: Clemens B
authors.initials: CB
authors.lastname: Caspar
authors.forename: Natalie
authors.initials: N
authors.lastname: Fischer
authors.forename: Sandro
authors.initials: S
authors.lastname: Anchisi
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Richard
authors.initials: R
authors.lastname: Cathomas
authors.forename: Jürg
authors.initials: J
authors.lastname: Bernhard
authors.forename: Nina M
authors.initials: NM
authors.lastname: Kotrubczik
authors.forename: Giannicola
authors.initials: G
authors.lastname: D'Addario
authors.forename: Christiane
authors.initials: C
authors.lastname: Pilop
authors.forename: Damien C
authors.initials: DC
authors.lastname: Weber
authors.forename: Stephan
authors.initials: S
authors.lastname: Bodis
authors.forename: Miklos
authors.initials: M
authors.lastname: Pless
authors.forename: Michael
authors.initials: M
authors.lastname: Mayer
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000503:physiopathology / Q000556:secondary / Q000628:therapy*; D010054:Brief Psychiatric Rating Scale; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D003071:Cognition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016371:Cranial Irradiation / Q000009:adverse effects / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D003606:Dacarbazine; D000077156:Gefitinib; D000077204:Temozolomide