MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma

被引：43

作者：

Sadones, J. ^{[1
]}

Michotte, A. ^{[1
]}

Veld, P. ^{[1
]}

Chaskis, C. ^{[1
]}

Sciot, R. ^{[2
]}

Menten, J. ^{[8
]}

Joossens, E. J. R. ^{[3
]}

Strauven, T. ^{[4
]}

D'Hondt, L. A. ^{[5
]}

Sartenaer, D. ^{[6
]}

Califice, S. F. E. H. ^{[7
]}

Bierau, K. ^{[7
]}

Svensson, C. ^{[7
]}

De Greve, J. ^{[1
]}

Neyns, B. ^{[1
]}

机构：

[1] UZ Brussel, B-1090 Brussels, Belgium

[2] Univ Ziekenhuis Leuven, B-3000 Louvain, Belgium

[3] Ziekenhuis Netwerk Middelheim, B-2020 Antwerp, Belgium

[4] AZ St Augustinus, B-2610 Antwerp, Belgium

[5] Ctr Hosp Notre Dame & Reine Fabiola, B-6000 Charleroi, Belgium

[6] Inst Pathol & Genet, Dept Genet, B-6041 Gosselies, Belgium

[7] OncoMethylome Sci SA, B-4000 Liege, Belgium

[8] Univ Ziekenhuis Gasthuisberg, B-3000 Louvain, Belgium

来源：

EUROPEAN JOURNAL OF CANCER | 2009年 / 45卷 / 01期

关键词：

Extended dosing; High-grade glioma; MGMT; Recurrent; Temozolomide; PHASE-II TRIAL; REPAIR GENE MGMT; DNA-REPAIR; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; PROGNOSTIC-FACTORS; METHYLATION; THERAPY; GLIOMA; RADIOTHERAPY;

D O I：

10.1016/j.ejca.2008.09.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aims: To investigate the correlation between O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma. Patients and methods: A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence. Results: A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p = 0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p < 0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma. Conclusions: MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：146 / 153

页数：8

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