Eventually, all patients with malignant gliomas recur or progress. Unfortunately, the optimal regimen in the salvage setting has not yet been defined. We retrospectively evaluated 52 patients with malignant gliomas who failed temozolomide therapy and were treated with a combination of intravenous carboplatin and oral cyclophosphamide. The median age of all patients, including those with glioblastoma multiforme (GBM) (n= 40) and anaplastic glioma (AG) (n= 12), was 45.5 years (range 23-68). All patients were treated with consolidation temozolomide after chemoradiotherapy. After temozolomide failure, second surgery was performed on 15, reirradiation on four and radiosurgery on three patients. The median number of chemotherapy cycles was 4 (range 1-8), the clinical benefit was 67.3%, a partial response was achieved in 26.9% and stable disease in 40.4%. In the GBM group, median progression-free survival (PFS) and overall survival (OS) were 3 (95% CI, 2.31-3.69) and 8 (95% CI, 4.76-11.24) months, respectively. In the AG group, median PFS and OS were 5 (95% CI, 3.51-6.49) and 11(95% CI, 6.38-15.62) months, respectively. The six-month PFS rate was 25%. Only one patient survived 18 months after treatment. Serious toxicity was mainly hematological.