Bevacizumab, a humanized monoclonal antibody that targets VEGF, was first approved in combination with chemotherapy for colorectal, lung, and breast cancers. Despite initial reluctance to evaluate bevacizumab in patients with brain tumors owing to concerns of intracranial hemorrhage, a series of 29 patients with recurrent malignant gliomas treated with bevacizumab and irinotecan showed no significant hemorrhage and an astounding radiographic response rate of 66%11compared with historical rates of 9%.12This led to more rigorous prospective clinical trials of bevacizumab in recurrent malignant gliomas (Table). The combination of bevacizumab and irinotecan was studied in single-arm phase 2 trials for recurrent anaplastic gliomas (n = 33) and GBM (n = 35), respectively, and showed response rates of 61% and 57% and progression-free survival (PFS) at 6 months of 55% and 46%.13,21These results compared favorably with historical rates of PFS at 6 months of 9% to 15% for recurrent GBM and 17% to 31% for recurrent anaplastic gliomas.12,20However, irinotecan had been previously tested as a single agent in phase 2 trials and showed radiographic response rates of only 2.5% to 6% and no improvement in PFS.22,23These studies raised the question of irinotecan's contribution to the bevacizumab combination regimen. We therefore conducted a phase 2 trial of single-agent bevacizumab for recurrent GBM. Forty-eight heavily pretreated patients were included and the radiographic response was 35% and the PFS at 6 months was 29%.10A large phase 2 trial randomized 167 patients with recurrent GBM to either single-agent bevacizumab or bevacizumab with irinotecan. This noncomparative randomized study showed response rates of 28% and 38%, respectively, and a PFS at 6 months of 43% and 50%, respectively.9In addition to the radiographic responses and prolongation of PFS, patients treated with bevacizumab often had less vasogenic edema and decreased corticosteroid dependence secondary to neutralization of VEGF, a known vascular permeability factor. Our data10combined with those of the single-agent bevacizumab arm of the randomized phase 2 trial9supported the accelerated approval of bevacizumab for recurrent or progressive GBM by the Food and Drug Administration.