ABSTRACT
OBJECT: Endothelial proliferation has been recognized as a marker of high-grade or aggressive glioma. Bevacizumab is a humanized immunoglobulin G1 monoclonal antibody to vascular endothelial growth factor that has been shown to have activity in malignant gliomas when combined with irinotecan. The authors report on a case series of 13 patients with recurrent heavily pretreated malignant glioma that was treated with the combination of bevacizumab and irinotecan. METHODS: Standard therapy with primary resection followed by adjuvant chemotherapy and radiation had failed in all patients. The median number of therapies applied, including initial surgery, was 5 (range 3-7 therapies). Nine patients were started on bevacizumab at a dose of 5 mg/m2 every 2 weeks. Four patients received bevacizumab at a dose of 10 mg/m2; irinotecan was given at a dose of 125 mg/m2 every week for 3 weeks. RESULTS: Of the 13 treated patients, 10 (77%) had a radiologically demonstrated partial response and 3 (23%) had stable disease. Six patients (46%) had a clinical response. The median time to disease progression while on treatment was 24 weeks. The median overall survival was 27 weeks. The disease progressed in 8 patients, despite an initial response. Five patients are still responding to therapy. Six of the 8 patients whose disease progressed have died. Bevacizumab was discontinued in 2 patients because of nonfatal intracranial bleeding. CONCLUSIONS: The combination of bevacizumab and irinotecan is safe and has excellent activity even in this relapsed, heavily pretreated population of patients with high-grade malignant glioma, most of whom would not be candidates for clinical trials.
