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

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 x 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 canmore » be used clinically without incurring normal tissue toxicities. Thus, information on lower doses of VEGF Trap and ionizing radiation is of clinical relevance.« less

Authors:
 [1];  [2];  [3];  [3];  [4];  [5];  [5];  [6]
  1. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA (United States). E-mail: Phyllis.Wachsberger@mail.tju.edu
  2. Department of Nutritional Sciences, University of Arizona, Tucson, AZ (United States)
  3. Department of Radiology, Thomas Jefferson University, Philadelphia, PA (United States)
  4. Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA (United States)
  5. Novartis, Emeryville, CA (United States)
  6. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA (United States)
Publication Date:
OSTI Identifier:
20951601
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2006.11.011; PII: S0360-3016(06)03394-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; COMBINED THERAPY; DRUGS; GLIOMAS; GROWTH; GROWTH FACTORS; IONIZING RADIATIONS; LIMBS; RADIATION DOSES; RADIOTHERAPY; RECEPTORS; TOXICITY

Citation Formats

Wachsberger, Phyllis R., Burd, Randy, Cardi, Chris, Thakur, Mathew, Daskalakis, Constantine, Holash, Jocelyn, Yancopoulos, George D., and Dicker, Adam P. VEGF Trap in Combination With Radiotherapy Improves Tumor Control in U87 Glioblastoma. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.11.011.
Wachsberger, Phyllis R., Burd, Randy, Cardi, Chris, Thakur, Mathew, Daskalakis, Constantine, Holash, Jocelyn, Yancopoulos, George D., & Dicker, Adam P. VEGF Trap in Combination With Radiotherapy Improves Tumor Control in U87 Glioblastoma. United States. doi:10.1016/j.ijrobp.2006.11.011.
Wachsberger, Phyllis R., Burd, Randy, Cardi, Chris, Thakur, Mathew, Daskalakis, Constantine, Holash, Jocelyn, Yancopoulos, George D., and Dicker, Adam P. Sun . "VEGF Trap in Combination With Radiotherapy Improves Tumor Control in U87 Glioblastoma". United States. doi:10.1016/j.ijrobp.2006.11.011.
@article{osti_20951601,
title = {VEGF Trap in Combination With Radiotherapy Improves Tumor Control in U87 Glioblastoma},
author = {Wachsberger, Phyllis R. and Burd, Randy and Cardi, Chris and Thakur, Mathew and Daskalakis, Constantine and Holash, Jocelyn and Yancopoulos, George D. and Dicker, Adam P.},
abstractNote = {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 x 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.},
doi = {10.1016/j.ijrobp.2006.11.011},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 67,
place = {United States},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}