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

To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma.A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence.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 (p0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma.MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.