Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly
The Lancet Oncology, 05/10/2012
Wick W et al. – Temozolomide alone is non–inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision–making.
Between May 15, 2005, and Nov 2, 2009, the authors enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65years, and a Karnofsky performance score of 60 or higher.
Patients were randomly assigned 100mg/m2 temozolomide, given on days 1-7 of 1week on, 1week off cycles, or radiotherapy of 60.0Gy, administered over 6-7weeks in 30 fractions of 1.8-2.0Gy.
The primary endpoint was overall survival.
They assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment.
Of 584 patients screened, the authors enrolled 412.
373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses.
Median overall survival was 8.6months (95% CI 7.3-10.2) in the temozolomide group versus 9.6months (8.2-10.8) in the radiotherapy group (hazard ratio [HR] 1.09, 95% CI 0.84-1.42, pnon-inferiority=0.033).
Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3.3months [95% CI 3.2-4.1] vs 4.7 [4.2-5.2]; HR 1.15, 95% CI 0.92-1.43, pnon-inferiority=0.043).
Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested.
MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11.9months [95% CI 9.0 to not reached] vs 8.2months [7.0-10.0]; HR 0.62, 95% CI 0.42-0.91, p=0.014).
EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8.4months [95e% CI 5.5—11.7] vs 4.6 [4.2—5.0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3.3 months [3.0-3.5] vs 4.6months [3.7-6.3]).
The most frequent grade 3-4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight).
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