Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.
BACKGROUND
Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety.


METHODS
Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival.


RESULTS
A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.


CONCLUSIONS
The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
Stupp
Roger
R
Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. roger.stupp@chuv.hospvd.ch
Mason
Warren P
WP
van den Bent
Martin J
MJ
Weller
Michael
M
Fisher
Barbara
B
Taphoorn
Martin J B
MJ
Belanger
Karl
K
Brandes
Alba A
AA
Marosi
Christine
C
Bogdahn
Ulrich
U
Curschmann
Jürgen
J
Janzer
Robert C
RC
Ludwin
Samuel K
SK
Gorlia
Thierry
T
Allgeier
Anouk
A
Lacombe
Denis
D
Cairncross
J Gregory
JG
Eisenhauer
Elizabeth
E
Mirimanoff
René O
RO
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011881:Radiotherapy, Computer-Assisted / Q000009:adverse effects; D016019:Survival Analysis; D000077204:Temozolomide
D000305:Adrenal Cortex Hormones; D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide