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Adjuvant Procarbazine, Lomustine, and
Vincristine Improves Progression-Free Survival but Not Overall
Survival in Newly Diagnosed Anaplastic Oligodendrogliomas and
Oligoastrocytomas: A Randomized European Organisation for Research and
Treatment of Cancer Phase III Trial
Martin J. van den Bent,
Antoine F. Carpentier, Alba A. Brandes, Marc
Sanson, Martin J.B. Taphoorn, Hans J.J.A.
Bernsen, Marc Frenay, Cees C. Tijssen,
Wolfgang Grisold, Laslo Sipos, Hanny
Haaxma-Reiche, Johannes M. Kros, Mathilde
C.M. van Kouwenhoven, Charles J. Vecht, Anouk
Allgeier, Denis Lacombe, Thierry Gorlia
From the Departments of Neurology
and Pathology, Daniel den Hoed Cancer Center/Erasmus University
Hospital, Rotterdam; Department of Neurology, Medical Center
Haaglanden/Westeinde Ziekenhuis, the Hague; Canisius Wilhemina
Ziekenhuis, Nijmegen; Department of Neurology, Elisabeth Gasthuis,
Tilburg; Department of Neurology, Academisch Ziekenhuis Groningen, the
Netherlands; Department of Neurology, Centre Hospitalier Universitaire
Pitié-Salpétrière, Paris; Department of Neurology, Centre Antoine
Lacassagne, Nice, France; Medical Oncology Department-Neurooncology
Unit, Azienda Ospedale-Università-Istituto Oncologico Veneto, Padova,
Italy; Ludwig Boltzmann Institute Neurooncology and Kaiser Franz Josef
Spital, Vienna, Austria; National Institute of Neurosurgery, Budapest,
Hungary; and European Organisation for Research and Treatment of
Cancer Data Center, Brussels, Belgium on behalf of the European
Organisation for Research and Treatment of Cancer Brain Tumor Group
and the Medical Research Council Clinical Trials Group.
Address reprint requests to Martin J. van den Bent, MD, Neuro-Oncology
Unit, Daniel den Hoed Oncology Center, PO Box 5201, 3008AE Rotterdam,
the Netherlands; e-mail: m.vandenbent@erasmusmc.nl
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Purpose. Anaplastic
oligodendrogliomas are more responsive to chemotherapy than
high-grade astrocytomas.
We investigated, in a multicenter randomized
controlled trial, whether adjuvant procarbazine, lomustine,
and vincristine (PCV) chemotherapy improves overall survival
(OS) in newly diagnosed patients with anaplastic oligodendrogliomas
or anaplastic oligoastrocytomas.
Patients and Methods. The
primary end point of the study was OS; secondary end points were
progression-free survival (PFS) and toxicity.
Patients were randomly assigned to either 59.4 Gy of
radiotherapy (RT) in 33 fractions only or to the same RT
followed by six cycles of standard PCV chemotherapy (RT/PCV).
1p and 19q deletions were assessed with fluorescent in situ
hybridization.
Results. A total of 368
patients were included.
The median follow-up time was 60 months, and 59% of
patients have died.
In the RT arm, 82% of patients with tumor progression
received chemotherapy.
In 38% of patients in the RT/PCV arm, adjuvant PCV was discontinued
for toxicity.
OS time after RT/PCV was 40.3 months compared with 30.6
months after RT only (P = .23).
RT/PCV increased PFS time compared with RT only (23 v
13.2 months, respectively; P = .0018).
Twenty-five percent of patients were diagnosed with combined
1p/19q loss; 74% of this subgroup was still alive after 60
months.
RT/PCV did not improve survival in the subgroup of patients
with 1p/19q loss.
Conclusion. Adjuvant PCV
chemotherapy does not prolong OS but does increase PFS in
anaplastic oligodendroglioma.
Combined loss of 1p/19q identifies a favorable subgroup of
oligodendroglial tumors.
No genetic subgroup could be identified that benefited with respect
to OS from adjuvant PCV.
Supported by the European
Organisation for Research and Treatment of Cancer (EORTC)
Translational Research Fund Grant No. TRF 01/02, by
AstraZeneca EORTC Translational Research Grant No. AZ/01/02,
and by Dutch Cancer Society Grant No. DDHK 2005-3416.
Presented in part at the 41st Annual
Meeting of the American Society of Clinical Oncology,
Orlando FL, May 13-17, 2005.
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