Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma.
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.
Kocher
Martin
M
Department of Radiotherapy, University Hospital, Cologne, Germany. martin.kocher@uk-koeln.de
Frommolt
Peter
P
Borberg
Sigrid Klara
SK
Rühl
Ursula
U
Steingräber
Maria
M
Niewald
Markus
M
Staar
Susanne
S
Stuschke
Martin
M
Becker
Gerd
G
Fischedick
Arnt-René
AR
Herfarth
Klaus
K
Grauthoff
Hermann
H
Müller
Rolf-Peter
RP
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
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide