Evaluation of Pre-radiotherapy Cyclophosphamide in Patients with Newly Diagnosed Glioblastoma Multiforme

Abstract

Cyclophosphamide is an alkylating agent that has shown activity in the treatment of pediatric brain tumors, including high-grade gliomas. This study was designed to evaluate the response of patients with newly diagnosed glioblastoma multiforme to pre-radiotherapy cyclophosphamide. Fourteen patients with glioblastoma multiforme were treated with high-dose cyclophosphamide (2 g/m²/day for 2 doses every 28 days) followed by either sargramostim or filgrastin. Sargramostim was given 250 µg/m² subcutaneously twice a day continuing through the leukocyte nadir until the absolute neutrophil count was more than 1000 cells/µl for 2 consecutive days. The filgrastin dose was 10 µg/kg given subcutaneously once daily until the post nadir absolute neutrophil count was ≥10,000 cells/µl. A total of 46 courses was given. Four patients received a total of 3 courses, 7 patients completed 4 courses and 3 patients received 2 courses. Three patients demonstrated complete response; 3 stable disease; and 8 progressive disease. The most common toxicity was hematologic, requiring platelet and packed red blood cell transfusions, with 13 admissions for neutropenia with fever. There were no deaths related to infection or bleeding. These results suggest that high-dose cyclophosphamide has modest activity with acceptable toxicity against newly diagnosed glioblastoma multiforme.