Bevacizumab versus bevacizumab plus vorinostat in adults with recurrent malignant glioma: Results of a phase I part of a phase I/II trial.

2029^ Background: Antiangiogenic therapy using b evacizumab (Bev) has shown promising activity against recurrent glioblastoma (GBM). However, most patients have disease progression after striking but transient responses. Salvage therapies have been uniformly ineffective, suggesting development of resistance mechanisms including upregulation of other proangiogenic factors and increased activity of hypoxia inducible factors (HIF)-1a. Vorinostat, a histone deacetylase (HDAC) inhibitor has single agent activity against recurrent GBM and downregulates HIF-1a and other proangiogenic and invasive factors. We hypothesized that HDAC inhibition combined with Bev would result in improved clinical outcome. We report the results of the Phase I portion of the study preceding the initiation of the 2-arm adaptive randomized Phase II study. Methods: Adults with recurrent malignant glioma, KPS ≥ 60, normal hepatic, renal and marrow organ function and no prior exposure to Bev or Vorinostat were enrolled to the combination t...