VEGF Trap in Combination With Radiotherapy Improves Tumor Control in U87 Glioblastoma

Phyllis R. Wachsberger, Randy M Burd, Chris Cardi, Mathew Thakur, Constantine Daskalakis, Jocelyn Holash, George D. Yancopoulos, Adam P. Dicker

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Purpose: To determine the effect of vascular endothelial growth factor VEGF Trap (Regeneron Pharmaceuticals, Tarrytown, NY), a humanized soluble vascular endothelial growth factor (VEGF) receptor protein, and radiation (RT) on tumor growth in U87 glioblastoma xenografts in nude mice. Methods and Materials: U87 cell suspensions were implanted subcutaneously into hind limbs of nude mice. VEGF Trap (2.5-25 mg/kg) was administered every 3 days for 3 weeks alone or in combination with a single dose of 10 Gy or fractionated RT (3 × 5 Gy). In addition, three scheduling protocols for VEGF Trap plus fractionated RT were examined. Results: Improved tumor control was seen when RT (either single dose or fractionated doses) was combined with the lowest dose of VEGF Trap (2.5 mg/kg). Scheduling did not significantly affect the efficacy of combined therapy. Although high-dose VEGF Trap (10 mg/kg or 25 mg/kg) significantly reduced tumor growth over that of RT alone, there was no additional benefit to combining high-dose VEGF Trap with RT. Conclusions: Vascular endothelial growth factor Trap plus radiation is clearly better than radiation alone in a U87 subcutaneous xenograft model. Although high doses of VEGF Trap alone are highly efficacious, it is unclear whether such high doses can be used clinically without incurring normal tissue toxicities. Thus, information on lower doses of VEGF Trap and ionizing radiation is of clinical relevance.

Original languageEnglish (US)
Pages (from-to)1526-1537
Number of pages12
JournalInternational Journal of Radiation Oncology Biology Physics
Volume67
Issue number5
DOIs
Publication statusPublished - Apr 1 2007

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Keywords

  • Anti-angiogenic
  • Radiotherapy
  • U87 glioblastoma
  • Vascular endothelial growth factor Trap

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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