Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme

We conducted a phase I study to determine (a) the maximum tolerated dose of peri-radiation therapy temozolomide (TMZ) and (b) the safety of a selected hypofractionated intensity modulated radiation therapy (HIMRT) regimen in glioblastoma multiforme (GBM) patients. Patients with histological diagnosis of GBM, Karnofsky performance status (KPS)≥ 60 and adequate bone marrow function were eligible for the study. All patients received peri-radiation TMZ; 1 week before the beginning of radiation therapy (RT), 1 week after RT and for 3 weeks during RT. Standard 75 mg/m(2)/day dose was administered to all patients 1 week post-RT. Dose escalation was commenced at level I: 50mg/m(2)/day, level II: 65 mg/m(2)/day and level III: 75 mg/m(2)/day for 4 weeks. HIMRT was delivered at 52.5 Gy in 15 fractions to the contrast enhancing lesion (or surgical cavity) plus the surrounding edema plus a 2 cm margin. Six men and three women with a median age of 67 years (range, 44-81) and a median KPS of 80 (range, 80-90) were enrolled. Three patients were accrued at each TMZ dose level. Median follow-up was 10 months (range, 1-15). Median progression free survival was 3.9 months (95% confidence interval [CI]: 0.9-7.4; range, 0.9-9.9 months) and the overall survival 12.7 months (95% CI: 2.5-17.6; range, 2.5-20.7 months). Time spent in a KPS ≥ 70 was 8.1 months (95% CI: 2.4-15.6; range, 2.4-16 months). No instance of irreversible grade 3 or higher acute toxicity was noted. HIMRT at 52.5 Gy in 15 fractions with peri-RT TMZ at a maximum tolerated dose of 75 mg/m(2)/day for 5 weeks is well tolerated and is able to abate treatment time for these patients.