High-grade gliomas are the most common primary brain tumors in adults. Twenty-seven patients with histopathologically proven anaplastic astrocytoma and glioblastoma multiforme were enrolled in this study from November 1998 to August 2002. Radiotherapy was administered after surgery and fotemustine (100 mg/m(2)) was sequentially administered every 3 weeks for 6 cycles. Overall, 111 cycles were administered to the 27 patients (median, 5 cycles; range, 1 to 6 cycles). Myelosuppression was mild to moderate. The median overall survival and progression free survival were 11 +/- 3.1 months (95%CI, 4.9-17.1) and 8 +/- 0.5 months (95%CI 7.1-8.9), respectively. One-year and two-year survivals were calculated at 48% and 7%, respectively. Significant prognostic factors (P<0.05) via univariate analysis were divided into two groups: completion of 6 cycles of chemotherapy versus incompletion of 6 cycles of chemotherapy. This trial demonstrates that postoperative radiotherapy and sequential fotemustine therapy is feasible, well tolerated, and may prolong survival in patients with newly diagnosed high-grade gliomas.