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Radiotherapy plus
Concomitant and Adjuvant Temozolomide for Glioblastoma
Roger Stupp, M.D.,
Warren P. Mason, M.D., Martin J. van den Bent, M.D., Michael Weller,
M.D., Barbara Fisher, M.D., Martin J.B. Taphoorn, M.D., Karl
Belanger, M.D., Alba A. Brandes, M.D., Christine Marosi, M.D.,
Ulrich Bogdahn, M.D., Jürgen Curschmann, M.D., Robert C. Janzer,
M.D., Samuel K. Ludwin, M.D., Thierry Gorlia, M.Sc., Anouk Allgeier,
Ph.D., Denis Lacombe, M.D., J. Gregory Cairncross, M.D., Elizabeth
Eisenhauer, M.D., René O. Mirimanoff, M.D., for the European
Organisation for Research and Treatment of Cancer Brain Tumor and
Radiotherapy Groups and the National Cancer Institute of Canada
Clinical Trials Group
From the Centre
Hospitalier Universitaire Vaudois, Lausanne, Switzerland (R.S.,
R-C.J., R.O.M.); Princess Margaret Hospital, Toronto (W.P.M.);
Daniel den Hoed Oncology Center–Erasmus University Medical Center
Rotterdam, Rotterdam, the Netherlands (M.J.B.); the University of Tübingen
Medical School, Tübingen, Germany (M.W.); the University of Western
Ontario, London, Ont., Canada (B.F.); the University Medical Center,
Utrecht, the Netherlands (M.J.B.T.); Hôpital Notre Dame du Centre
Hospitalier Universitaire, Montreal (K.B.); Azienda-Ospedale
Università, Padova, Italy (A.A.B.); Medical University of Vienna,
Vienna (C.M.); Universitätskliniken, Regensburg, Germany (U.B.);
Inselspital, Bern, Switzerland (J.C.); Queen's University, Kingston,
Ont., Canada (S.K.L.); the European Organisation for Research and
Treatment of Cancer Data Center, Brussels (T.G., A.A., D.L.); the
University of Calgary, Calgary, Alta., Canada (J.G.C.); and the
National Cancer Institute of Canada Clinical Trials Group, Kingston,
Ont., Canada (E.E.).
Address reprint requests to Dr. Stupp at the Multidisciplinary
Oncology Center, Centre Hospitalier Universitaire Vaudois, 46, rue
du Bugnon, CH-1011 Lausanne, Switzerland, or at
roger.stupp@chuv.hospvd.ch.
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.
Abstract
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