Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951

Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT). Adult patients with newly diagnosed anapl...

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Published inJournal of clinical oncology Vol. 31; no. 3; pp. 344 - 350
Main Authors van den Bent, Martin J., Brandes, Alba A., Taphoorn, Martin J.B., Kros, Johan M., Kouwenhoven, Mathilde C.M., Delattre, Jean-Yves, Bernsen, Hans J.J.A., Frenay, Marc, Tijssen, Cees C., Grisold, Wolfgang, Sipos, László, Enting, Roelien H., French, Pim J., Dinjens, Winand N.M., Vecht, Charles J., Allgeier, Anouk, Lacombe, Denis, Gorlia, Thierry, Hoang-Xuan, Khê
Format Journal Article
LanguageEnglish
Published Alexandria, VA American Society of Clinical Oncology 20.01.2013
Subjects
Online AccessGet full text
ISSN0732-183X
1527-7755
1527-7755
DOI10.1200/JCO.2012.43.2229

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Abstract Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT). Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis. A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance. The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors.
AbstractList Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT). Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis. A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance. The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors.
Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT).PURPOSEAnaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT).Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis.PATIENTS AND METHODSAdult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis.A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance.RESULTSA total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance.The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors.CONCLUSIONThe addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors.
Author László Sipos
Pim J. French
Alba A. Brandes
Martin J.B. Taphoorn
Anouk Allgeier
Martin J. van den Bent
Thierry Gorlia
Charles J. Vecht
Cees C. Tijssen
Wolfgang Grisold
Johan M. Kros
Roelien H. Enting
Winand N.M. Dinjens
Mathilde C.M. Kouwenhoven
Khê Hoang-Xuan
Marc Frenay
Denis Lacombe
Jean-Yves Delattre
Hans J.J.A. Bernsen
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  organization: Martin J. van den Bent, Johan M. Kros, Mathilde C.M. Kouwenhoven, Roelien H. Enting, Pim J. French, and Winand N.M. Dinjens, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam; Martin J.B. Taphoorn and Charles J. Vecht, Medical Center Haaglanden, The Hague; Martin J.B. Taphoorn, Vrije Universiteit Medisch Centrum, Amsterdam; Hans J.J.A. Bernsen, Canisius Wilhelmina Ziekenhuis, Nijmegen; Cees C. Tijssen, St Elisabeth Hospital, Tilburg; Roelien H. Enting, University Medical Center Groningen, Groningen
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  givenname: Thierry
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  fullname: Gorlia, Thierry
  organization: Martin J. van den Bent, Johan M. Kros, Mathilde C.M. Kouwenhoven, Roelien H. Enting, Pim J. French, and Winand N.M. Dinjens, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam; Martin J.B. Taphoorn and Charles J. Vecht, Medical Center Haaglanden, The Hague; Martin J.B. Taphoorn, Vrije Universiteit Medisch Centrum, Amsterdam; Hans J.J.A. Bernsen, Canisius Wilhelmina Ziekenhuis, Nijmegen; Cees C. Tijssen, St Elisabeth Hospital, Tilburg; Roelien H. Enting, University Medical Center Groningen, Groningen
– sequence: 19
  givenname: Khê
  surname: Hoang-Xuan
  fullname: Hoang-Xuan, Khê
  organization: Martin J. van den Bent, Johan M. Kros, Mathilde C.M. Kouwenhoven, Roelien H. Enting, Pim J. French, and Winand N.M. Dinjens, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam; Martin J.B. Taphoorn and Charles J. Vecht, Medical Center Haaglanden, The Hague; Martin J.B. Taphoorn, Vrije Universiteit Medisch Centrum, Amsterdam; Hans J.J.A. Bernsen, Canisius Wilhelmina Ziekenhuis, Nijmegen; Cees C. Tijssen, St Elisabeth Hospital, Tilburg; Roelien H. Enting, University Medical Center Groningen, Groningen
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Issue 3
Keywords Antineoplastic agent
Procarbazine
Nervous system diseases
Nitrosoureas
Adjuvant treatment
Early stage
Long term
Intracranial tumor
Vincristine
Anaplastic oligodendroglioma
Cerebral disorder
Alkylating agent
Alkaloid
Chemotherapy
Treatment
Cancerology
Follow up study
Nitrogen mustard
Central nervous system disease
Lomustine
Antimitotic
European Organization for Research and Treatment of Cancer
Language English
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PublicationTitle Journal of clinical oncology
PublicationTitleAlternate J Clin Oncol
PublicationYear 2013
Publisher American Society of Clinical Oncology
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23149899 - Nat Rev Clin Oncol. 2012 Dec;9(12):670. doi: 10.1038/nrclinonc.2012.198.
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– reference: 23149899 - Nat Rev Clin Oncol. 2012 Dec;9(12):670. doi: 10.1038/nrclinonc.2012.198.
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Snippet Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition...
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SubjectTerms Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Biological and medical sciences
Brain Neoplasms - drug therapy
Brain Neoplasms - genetics
Brain Neoplasms - radiotherapy
Chemotherapy, Adjuvant
Disease-Free Survival
Follow-Up Studies
Gene Deletion
Humans
In Situ Hybridization, Fluorescence
Kaplan-Meier Estimate
Lomustine - administration & dosage
Lomustine - adverse effects
Medical sciences
Neurology
Oligodendroglioma - drug therapy
Oligodendroglioma - genetics
Oligodendroglioma - radiotherapy
Procarbazine - administration & dosage
Procarbazine - adverse effects
Tumors
Tumors of the nervous system. Phacomatoses
Vincristine - administration & dosage
Vincristine - adverse effects
Title Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951
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