title: Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma.
abstract: OBJECTIVE
  To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients.
  
  
  METHODS
  From February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age (< or =/>50 years) and WHO performance score (0-1 vs. 2). RT consisted of 60 Gy in 30 fractions. In the RT + TMZ arm, oral TMZ was administered daily at a dose of 75 mg/m(2) including weekends (40-42 doses). Adjuvant treatment was not given, but in both arms, patients with recurrent tumors and in good condition (WHO 0-2) were scheduled for salvage chemotherapy with TMZ.
  
  
  RESULTS
  The trial was stopped early due to the results of EORTC-study 26981-22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone. In total, 62/65 patients were evaluable. Stratification variables were well balanced (< or = 50 years 26% vs. 20%, WHO 0-1 91% vs. 100%). Neither overall survival (median 17 vs. 15 months) nor progression-free survival (median 7 vs. 6 months) differed significantly between the two arms. In the RT (RT + TMZ) arm, 76% (62%) of the progressing patients received salvage chemotherapy with TMZ, 36% (50%) had a second resection. There was a time-constant trend for increased general quality of life (EORTC questionnaire QLQ C30) and brain-specific quality of life (EORTC questionnaire B20) in the combined arm. Lymphopenia G3-4 was more frequent (33 vs. 6%) in the RT + TMZ arm.
  
  
  CONCLUSIONS
  After early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival.
authors.affiliation: Department of Radiotherapy, University Hospital, Cologne, Germany. martin.kocher@uk-koeln.de
authors.forename: Martin
authors.initials: M
authors.lastname: Kocher
authors.forename: Peter
authors.initials: P
authors.lastname: Frommolt
authors.forename: Sigrid Klara
authors.initials: SK
authors.lastname: Borberg
authors.forename: Ursula
authors.initials: U
authors.lastname: Rühl
authors.forename: Maria
authors.initials: M
authors.lastname: Steingräber
authors.forename: Markus
authors.initials: M
authors.lastname: Niewald
authors.forename: Susanne
authors.initials: S
authors.lastname: Staar
authors.forename: Martin
authors.initials: M
authors.lastname: Stuschke
authors.forename: Gerd
authors.initials: G
authors.lastname: Becker
authors.forename: Arnt-René
authors.initials: AR
authors.lastname: Fischedick
authors.forename: Klaus
authors.initials: K
authors.lastname: Herfarth
authors.forename: Hermann
authors.initials: H
authors.lastname: Grauthoff
authors.forename: Rolf-Peter
authors.initials: RP
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001772:Blood Cell Count; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004992:Ethics, Medical; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D018579:Patient Selection; D011788:Quality of Life; D011879:Radiotherapy Dosage; D016879:Salvage Therapy; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide