LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is 
well tolerated in patients with recurrent glioblastoma.Treatment of recurrent 
glioblastoma remains challenging as this study and others attempt to improve 
progression-free survival and overall survival with BEV-containing regimens.
BACKGROUND: Recurrent glioblastoma (GBM; World Health Organization grade 4) 
continues to have a very poor prognosis. Bevacizumab (BEV) has been shown to 
improve progression-free survival (PFS) in recurrent GBM and is approved by the 
U.S. Food and Drug Administration for the treatment of recurrent GBM. 
Combination regimens have been explored, and in this phase II nonrandomized 
trial, we evaluated the efficacy of BEV combined with histone deacetylase 
inhibitor vorinostat (VOR) in recurrent GBM.
MATERIALS AND METHODS: In this phase II, single-center, nonrandomized study, 
subjects with recurrent GBM received BEV 10 mg/kg intravenously (IV) every 2 
weeks combined with VOR 400 mg p.o. daily for 7 days on, 7 days off, in a 28-day 
cycle. The primary endpoint was 6-month PFS (PFS6).
RESULTS: Forty patients with recurrent GBM were enrolled and evaluated. PFS6 was 
30.0% (95% confidence interval [CI] 16.8%-44.4%). Median overall survival (OS) 
was 10.4 months (95% CI 7.6-12.8 months). Overall radiographic response rate was 
22.5% based on 9 partial responses. The most common grade 2 and above 
treatment-related adverse events were lymphopenia (55%), leukopenia (45%), 
neutropenia (35%), and hypertension (33%). Grade 4 adverse events were 
leukopenia (3%), neutropenia (3%), sinus bradycardia (3%), and venous 
thromboembolism (3%). Two deaths occurred in this study, with one due to tumor 
progression and another possibly related as death not otherwise specified.
CONCLUSION: Combination treatment of BEV and VOR was well tolerated. This 
combination therapy for this study population did not improve PFS6 or median OS 
when compared with BEV monotherapy.