Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma

Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):383-9. doi: 10.1016/j.ijrobp.2008.05.062.

Abstract

Introduction: 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 and materials: 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.

Conclusion: 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.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Bevacizumab
  • Blood Volume / drug effects
  • Brain Neoplasms* / blood supply
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / radiotherapy
  • Cerebrovascular Circulation / drug effects
  • Combined Modality Therapy / methods
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Feasibility Studies
  • Female
  • Glioma* / blood supply
  • Glioma* / drug therapy
  • Glioma* / radiotherapy
  • Humans
  • Male
  • Middle Aged
  • Radiotherapy Dosage
  • Temozolomide
  • Vascular Endothelial Growth Factor Receptor-2 / analysis

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Alkylating
  • Bevacizumab
  • Dacarbazine
  • Vascular Endothelial Growth Factor Receptor-2
  • Temozolomide