title: Enzastaurin before and concomitant with radiation therapy, followed by enzastaurin maintenance therapy, in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation.
abstract: BACKGROUND
  This study's primary objective was evaluation of the progression-free survival rate at 6 months (PFS-6) in patients with newly diagnosed glioblastoma without O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter hypermethylation postsurgically treated with enzastaurin before and concomitantly with radiation therapy, followed by enzastaurin maintenance therapy. PFS-6 of at least 55% was set to be relevant compared with the data of the EORTC 26981/22981 NCIC CE.3 trial.
  
  
  METHODS
  Adult patients with a life expectancy of at least 12 weeks who were newly diagnosed with a histologically proven supratentorial glioblastoma without MGMT promoter hypermethylation were eligible. Patients were treated with enzastaurin prior to, concomitantly with, and after standard partial brain radiotherapy. Here we report on a multicenter, open-label, uncontrolled phase II study of patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation treated with enzastaurin and radiation therapy within 4 study periods.
  
  
  RESULTS
  PFS-6 was 53.6% (95% confidence interval [CI]: 39.8-65.6). The median overall survival was 15.0 months (95% CI: 11.9-17.9) for all patients, 3.9 months (95% CI: 0.8-9.0) for patients with biopsy, 15.4 months (95% CI: 10.1-17.9) for patients with partial resection, and 18.9 months (95% CI: 13.9-28.5) for patients with complete resection. The safety profile in this study was as expected from previous trials, and the therapy was well tolerated.
  
  
  CONCLUSIONS
  PFS-6 missed the primary planned outcome of 55%. The secondary exploratory analysis according to resection status of the different subgroups of patients with biopsies, partial resection, and complete resection demonstrates the strong prognostic influence of resection on overall survival.
authors.affiliation: Corresponding Author: Wolfgang Wick, MD, Department of Neurooncology, National Center for Tumor Diseases and Neurology Clinic, University Clinic Heidelberg and German Cancer Research Centre, Im Neuenheimer Feld 400, 69120-Heidelberg, Germany. wolfgang.wick@med.uni-heidelberg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Peipei
authors.initials: P
authors.lastname: Shei
authors.forename: Valerie
authors.initials: V
authors.lastname: Moreau-Donnet
authors.forename: Clemens
authors.initials: C
authors.lastname: Stoffregen
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000628:therapy*; D059248:Chemoradiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D007211:Indoles; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; C504878:enzastaurin
keywords: MGMT; brain tumors; enzastaurin; glioblastoma; radiotherapy
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