VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma.
OBJECTIVE
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
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.
Wachsberger
Phyllis R
PR
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Phyllis.Wachsberger@mail.tju.edu
Burd
Randy
R
Cardi
Chris
C
Thakur
Mathew
M
Daskalakis
Constantine
C
Holash
Jocelyn
J
Yancopoulos
George D
GD
Dicker
Adam P
AP
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000187:drug effects / Q000528:radiation effects; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects; D019275:Radiopharmaceuticals; D011879:Radiotherapy Dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D014183:Transplantation, Heterologous; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D009363:Neoplasm Proteins; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; D042442:Vascular Endothelial Growth Factors; D019788:Fluorodeoxyglucose F18