Glioblastoma (GBM) is the commonest primary brain tumor in adult and it carries the worst prognosis. Atorvastatin is an inhibitor of HMG-CoA reductase, a rate limiting enzyme in the mevalonate pathway. Preclinical studies demonstrate encouraging anticancer activity of statins.
In this open-label, prospective, single-arm, phase II study, eligible patients received oral Atorvastatin (40 mg/d for 3 weeks and 80 mg/d thereafter) in combination with standard therapy comprising radiotherapy (60 Gy/30 fractions) and TMZ (75 mg/m2/d) in the 6-wk concurrent phase, then with TMZ (150-200 mg/m2/d on days 1-5 for 6 cycles). The primary endpoint is progression free survival (PFS) at 6 months. A minimum of 80% power required at least 32 eligible patients with planned interim analysis after the first 15 evaluable patients.
From January 2014, 20 of 32 planned patients have received therapy and the first 15 evaluable patients were included in this planned interim analysis. Median age was 48 (20-69); 28% were ≥ 60 years of age and 61% were male. 95% of patients underwent resection and 5% had biopsy only. Patients had median and minimum follow-up of 11.6 months and 6 months, respectively. PFS-6 rate was 67% with median PFS of 9.1 months. Median overall survival has not yet been reached to date. Grades 3 and 4 hematological adverse events occurred in 33% of patients. Three patient died due to disease progression.
This is the first clinical trial investigating statins in combination with standard therapy (RT and TMZ) in newly diagnosed GBM patients. Planned interim analysis appears promising and it met criteria for continued accrual.To date, the treatment was safe in this patient population. clinical trial information: NCT02029573
Clinical trial identification
Legal entity responsible for the study
Ministry of Health, Saudi Arabia
King Fahad Medical City
All authors have declared no conflicts of interest.