Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Neuro-Oncology Unit, Erasmus MC-Daniel den Hoed Cancer Center, PO Box 5201, 3008AE Rotterdam, The Netherlands. m.vandenbent@erasmusmc.nl
Martin J
MJ
van den Bent
Alba A
AA
Brandes
Martin J B
MJ
Taphoorn
Johan M
JM
Kros
Mathilde C M
MC
Kouwenhoven
Jean-Yves
JY
Delattre
Hans J J A
HJ
Bernsen
Marc
M
Frenay
Cees C
CC
Tijssen
Wolfgang
W
Grisold
László
L
Sipos
Roelien H
RH
Enting
Pim J
PJ
French
Winand N M
WN
Dinjens
Charles J
CJ
Vecht
Anouk
A
Allgeier
Denis
D
Lacombe
Thierry
T
Gorlia
Khê
K
Hoang-Xuan
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine