Phase II study of chemotherapy with ACNU plus cisplatin followed by cranial irradiation in patients with newly diagnosed glioblastoma multiforme

Purpose: To evaluate the efficacy and toxicity of chemotherapy with ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3-nitrosourea) plus cisplatin followed by cranial irradiation in patients with newly diagnosed glioblastoma multiforme. Patients and methods: Between August 1999 and July 2001, previously untreated 30 patients with histologically confirmed glioblastoma multiforme were treated. Chemotherapy consisting of up to 2 cycles of 72 h of continuous intravenous infusion of ACNU (40 mg/m²/day) and cisplatin (40 mg/m²/d) was given over a 6-week period. Radiation was begun 6 weeks after the second cycle of chemotherapy. Results: Median age was 48 years (range 18-66 years) and 22 patients with residual measurable disease after surgery were eligible for response analysis. One (5%) had a complete response (CR), 36% partial response (PR), 14% stable disease (SD), and 45% progressive disease (PD) after chemotherapy. After additional radiation, 22% had CR, 22% PR, 16% SD, and 42% PD. Grades III and IV leukopenia and thrombocytopenia occurred in 18 cycles (36%) and 15 cycles (30%), respectively. No fatal complications occurred. Median time to progression was 5.9 months (95% CI 5.1-6.8 months) and median overall survival was 14.9 months (95% CI 9.1-20.7 months). Conclusions: Preradiation chemotherapy with ACNU plus cisplatin is effective and feasible in patients with glioblastoma multiforme.