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

Journal Article · Sun Apr 01 04:00:00 EDT 2007 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2006.11.011· OSTI ID:20951601

Wachsberger, Phyllis R ^[1]; Burd, Randy ^[2]; Cardi, Chris ^[3]; Thakur, Mathew ^[3]; Daskalakis, Constantine ^[4]; Holash, Jocelyn ^[5]; Yancopoulos, George D ^[5]; Dicker, Adam P ^[1]

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1. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA (United States)
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)

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.

• OSTI ID: 20951601
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 67; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
COMBINED THERAPY
DRUGS
GLIOMAS
GROWTH
GROWTH FACTORS
IONIZING RADIATIONS
LIMBS
RADIATION DOSES
RADIOTHERAPY
RECEPTORS
TOXICITY