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Clinical Trial
. 2011 Mar;13(3):317-23.
doi: 10.1093/neuonc/noq191.

Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group

Kenneth J Cohen  1 , Ian F Pollack, Tianni Zhou, Allen Buxton, Emiko J Holmes, Peter C Burger, Daniel J Brat, Marc K Rosenblum, Ronald L Hamilton, Robert S Lavey, Richard L Heideman
Affiliations
Clinical Trial

Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group

Kenneth J Cohen et al. Neuro Oncol. 2011 Mar.

Abstract

To determine whether temozolomide is an active agent in the treatment of children with high-grade astrocytomas and whether survival is influenced by the expression of the O6-methylguanine-methyltransferase gene (MGMT) in these patients. In the Children's Oncology Group study ACNS0126, 107 patients with a diagnosis of anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), or gliosarcoma were enrolled. All patients underwent concomitant chemoradiotherapy with temozolomide, followed by adjuvant chemotherapy with temozolomide. The outcomes were compared with those of children treated in Children's Cancer Group (CCG) study CCG-945. Formalin-fixed, paraffin-embedded tumor tissue was available in 71 cases for immunohistochemical analysis of MGMT expression. Ninety patients were deemed eligible, 31 with AA, 55 with GBM, and 4 with other eligible diagnoses. The 3-year event-free survival (EFS) and overall survival (OS) rates were 11 ± 3% and 22 ± 5%, respectively. There was no evidence that temozolomide given during radiation therapy and as adjuvant therapy resulted in improved EFS compared with that found in CCG-945 (p = 0.98). The 3-year EFS rate for AA was 13 ± 6% in ACNS0126 compared with 22 ± 5.5% in CCG-945 (p = 0.95). The 3-year EFS rate for GBM was 7 ± 4% in ACNS0126 compared with 15 ± 5% in CCG-945 (p = 0.77). The 2-year EFS rate was 17 ± 5% among patients without MGMT overexpression and 5 ± 4% among those with MGMT overexpression (p = 0.045). Temozolomide failed to improve outcome in children with high-grade astrocytomas. MGMT overexpression was adversely associated with survival.

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Figures

Fig. 1.
Fig. 1.
EFS and OS rates of HGG patients enrolled in ACNS0126.
Fig. 2.
Fig. 2.
EFS comparison of ACNS0126 and CCG-945. PCM, parametric cure model.
Fig. 3.
Fig. 3.
EFS comparison as a function of MGMT expression (no overexpression: 0, 1, and 2; overexpression: 3 and 4).
See this image and copyright information in PMC

Comment in

References

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