Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma.
BACKGROUND
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma.


METHODS
Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed.


RESULTS
Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively.


CONCLUSIONS
Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.
Narayana
Ashwatha
A
Department of Radiation Oncology, New York University Medical Center, New York, NY 11016, USA. ashwatha.narayana@nyumc.org
Golfinos
John G
JG
Fischer
Ingeborg
I
Raza
Shahzad
S
Kelly
Patrick
P
Parker
Erik
E
Knopp
Edmond A
EA
Medabalmi
Praveen
P
Zagzag
David
D
Eagan
Patricia
P
Gruber
Michael L
ML
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000068258:Bevacizumab; D001810:Blood Volume / Q000187:drug effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000532:radiotherapy; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D000077204:Temozolomide; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating; D000068258:Bevacizumab; D003606:Dacarbazine; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077204:Temozolomide