Safety of thrice-daily hyperfractionated radiation and BCNU for high-grade gliomas

Purpose: To investigate the safety of thrice-daily hyperfractionated radiotherapy (RT) given in conjunction with BCNU (carmustine) in high-grade gliomas. Methods and Materials: Patients >18 years old with newly diagnosed high-grade gliomas were eligible. The dose of radiation was 5040 cGy, with a 1440-cGy boost in 180 cGy fractions delivered thrice daily in two 6-day periods with a 2-week interval. BCNU (200 mg/m²) was administered on the first day of radiation, then every 7 weeks for 1 year and every 10 weeks for another year. Results: Eighteen patients were enrolled. The mean age was 49.6 years. Sixteen patients had astrocytomas (Grade 3 or 4 in 5 and 11 patients, respectively) and 2 had oligoastrocytomas (Grade 3 and 4 in 1 patient each). One underwent total resection, 9 subtotal resection, and 8 biopsy only. Thirteen patients had stable disease, 4 regression, and 1 progression. The median time to progression was 37.8 weeks. The median overall survival was 44.4 weeks. Nine patients had neurologic toxicities, including 2 deaths at 69 and 139 weeks. Conclusion: This regimen is unacceptably toxic. Factors that could have contributed to the toxicity may include the total radiation dose, thrice-daily hyperfractionation, and the concurrent use of i.v. BCNU.