Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.
Level 2 - randomized trial
Multicenter phase III randomized controlled trial
PubMed 15758009 · doi:10.1056/NEJMoa043330
What was done
A total of 573 patients across 85 centers with newly diagnosed, histologically confirmed glioblastoma (median age 56 years, 84% with prior debulking surgery) were randomized to receive radiotherapy alone (60 Gy in 2 Gy daily fractions over 6 weeks) or radiotherapy plus continuous daily temozolomide (75 mg/m²/day throughout radiotherapy) followed by 6 cycles of adjuvant temozolomide (150–200 mg/m² for 5 days per 28-day cycle). The primary endpoint was overall survival.
What was found
At a median follow-up of 28 months, median survival was 14.6 months with radiotherapy plus temozolomide versus 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death was 0.63 (95% CI, 0.52 to 0.75; P < 0.001). The two-year survival rate was 26.5% with temozolomide plus radiotherapy versus 10.4% with radiotherapy alone. Concomitant temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7% of patients.
Why it matters
This landmark trial established concomitant and adjuvant temozolomide added to radiotherapy as the global standard of care for newly diagnosed glioblastoma. It demonstrated a clear, statistically significant survival benefit over radiotherapy alone.
Limits
Absolute median survival extension was modest (2.5 months), and two-year mortality remained high (73.5%). The abstract does not report performance status breakdown, quality-of-life measures, or molecular biomarkers such as MGMT promoter methylation status.
Cited by
- contradicts There has been no major advancement in the clinical management of glioblastoma in 100 years.