BACKGROUND: A recent randomized study conducted on newly diagnosed glioblastoma (GBM) patients demonstrated that concomitant and adjuvant temozolomide added to standard radiotherapy had a survival advantage compared with radiotherapy alone. The overall survival benefit of this aggressive treatment, however, was attenuated in older or poor performance status patients. The aim of the present study was to verify the activity and the toxicity of temozolomide administration concurrent and adjuvant to radiotherapy as first‐line treatment for elderly GBM patients, and to explore correlations between clinical outcome and O6 methylguanine‐DNA methyltransferase (MGMT) promoter methylation status. METHODS: Newly diagnosed GBM patients ≥65 years were considered eligible. Treatment comprised radiotherapy (60 Gy in 30 fractions over 6 weeks) plus continuous daily temozolomide (75 mg/m2/day), followed by 12 maintenance temozolomide cycles (150 mg/m2 once a day for 5 consecutive days every 28 days) if MRI showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. RESULTS: A total of 58 patients (34 males; median age, 68 years; range, 65‐82 years) were enrolled. Sixteen patients (43%) presented MGMT promoter methylated and 21 unmethylated (57%) status. The median progression‐free survival and median survival time (MST) were 9.5 months (95% confidence interval [CI], 8.6‐10.5) and 13.7 months (95% CI, 10‐17.3 months), respectively. Mental status deterioration grade 3‐4 was detected in 25% of patients. Leukoencephalopathy was diagnosed in 10% of patients. CONCLUSIONS: The overall and progression‐free survival of patients given concomitant and adjuvant temozolomide are greater than in those given radiotherapy alone; however, this regimen incurs a greater deterioration in mental status. Further randomized trials should, therefore, be conducted to investigate the efficacy and against the toxicity of this regimen as first‐line therapy in patients with GBM. Cancer 2009. © 2009 American Cancer Society.

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.