Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02) Journal Article


Authors: Iwamoto, F. M.; Lamborn, K. R.; Robins, H. I.; Mehta, M. P.; Chang, S. M.; Butowski, N. A.; Deangelis, L. M.; Abrey, L. E.; Zhang, W. T.; Prados, M. D.; Fine, H. A.
Article Title: Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02)
Abstract: The objective of this phase II single-arm study was to evaluate the efficacy and safety of pazopanib, a multitargeted tyrosine kinase inhibitor, against vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet-derived growth factor receptor-α and -β, and c-Kit, in recurrent glioblastoma. Patients with ≤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 ≥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. Singleagent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses. ClinicalTrials.gov identifier: NCT00459381. © The Author(s) 2010.
Keywords: vasculotropin receptor 3; adult; clinical article; treatment outcome; aged; middle aged; clinical trial; constipation; disease course; fatigue; mortality; neutropenia; cancer recurrence; angiogenesis inhibitor; diarrhea; drug dose reduction; drug efficacy; drug safety; hypertension; hypophosphatemia; side effect; nuclear magnetic resonance imaging; brain tumor; brain neoplasms; magnetic resonance imaging; anorexia; platelet derived growth factor alpha receptor; stem cell factor; progression free survival; multiple cycle treatment; phase 2 clinical trial; neoplasm recurrence, local; anemia; leukopenia; nausea; thrombocytopenia; clinical assessment; weight reduction; pathology; pyrimidines; vasculotropin receptor 2; neovascularization, pathologic; vascularization; abdominal pain; arthralgia; flushing; hyperglycemia; lymphocytopenia; pruritus; hypermagnesemia; hypoalbuminemia; hypokalemia; hyponatremia; disease progression; sulfonamide; multicenter study; thromboembolism; tumor recurrence; sulfonamides; thrombosis; glioblastoma; pancreatitis; pazopanib; peripheral edema; limb pain; hyperbilirubinemia; heartburn; headache; hypercholesterolemia; embolism; pyrimidine derivative; flatulence; hand foot syndrome; administration, oral; dry skin; angiogenesis inhibitors; epistaxis; neovascularization (pathology); brain hemorrhage; proteinuria; vasculotropin receptor 1; ulcer; oral drug administration; platelet derived growth factor beta receptor; abdominal distension; hypopigmentation; antiangiogenesis; clinical therapy trials; giloblastoma; ducubitus ulcer; excessive sweating; gastritis; sweating
Journal Title: Neuro-Oncology
Volume: 12
Issue: 8
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2010-08-01
Start Page: 855
End Page: 861
Language: English
DOI: 10.1093/neuonc/noq025
PUBMED: 20200024
PROVIDER: scopus
PMCID: PMC2940686
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: NEURJ" - "Source: Scopus"
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  1. Lauren E Abrey
    276 Abrey