Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas Journal Article


Authors: Nayak, L.; de Groot, J.; Wefel, J. S.; Cloughesy, T. F.; Lieberman, F.; Chang, S. M.; Omuro, A.; Drappatz, J.; Batchelor, T. T.; DeAngelis, L. M.; Gilbert, M. R.; Aldape, K. D.; Yung, A. W. K.; Fisher, J.; Ye, X.; Chen, A.; Grossman, S.; Prados, M.; Wen, P. Y.
Article Title: Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas
Abstract: Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24–69); median KPS 90 (60–100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1–16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks. © 2017, Springer Science+Business Media New York.
Keywords: temozolomide; aflibercept; dose-dense; vegf trap; newly diagnosed glioblastoma
Journal Title: Journal of Neuro-Oncology
Volume: 132
Issue: 1
ISSN: 0167-594X
Publisher: Springer  
Date Published: 2017-03-01
Start Page: 181
End Page: 188
Language: English
DOI: 10.1007/s11060-016-2357-9
PROVIDER: scopus
PUBMED: 28116649
PMCID: PMC5588922
DOI/URL:
Notes: Article -- Export Date: 4 April 2017 -- Source: Scopus
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MSK Authors
  1. Antonio Marcilio Padula Omuro
    200 Omuro