The objective of this phase II single-arm study was to evaluate the efficacy and 
safety of pazopanib, a multi-targeted tyrosine kinase inhibitor, against 
vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, 
platelet-derived growth factor receptor-alpha and -beta, and c-Kit, in recurrent 
glioblastoma. Patients with < or =2 relapses and no prior anti-VEGF/VEGFR 
therapy were treated with pazopanib 800 mg daily on 4-week cycles without 
planned interruptions. Brain magnetic resonance imaging and clinical 
reassessment were made every 8 weeks. The primary endpoint was efficacy as 
measured by 6-month progression-free survival (PFS6). Thirty-five GBM patients 
with a median age of 53 years and median Karnofsky performance scale of 90 were 
accrued. Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), 
thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS 
hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 
patients required dose reduction. Two patients had a partial radiographic 
response by standard bidimensional measurements, whereas 9 patients (6 at the 
8-week point and 3 only within the first month of treatment) had decreased 
contrast enhancement, vasogenic edema, and mass effect but <50% reduction in 
tumor. The median PFS was 12 weeks (95% confidence interval [CI]: 8-14 weeks) 
and only 1 patient had a PFS time > or =6 months (PFS6 = 3%). Thirty patients 
(86%) had died and median survival was 35 weeks (95% CI: 24-47 weeks). Pazopanib 
was reasonably well tolerated with a spectrum of toxicities similar to other 
anti-VEGF/VEGFR agents. Single-agent pazopanib did not prolong PFS in this 
patient population but showed in situ biological activity as demonstrated by 
radiographic responses. ClinicalTrials.gov identifier: NCT00459381.