Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas Journal Article


Authors: Gutin, P. H.; Iwamoto, F. M.; Beal, K.; Mohile, N. A.; Karimi, S.; Hou, B. L.; Lymberis, S.; Yamada, Y.; Chang, J.; Abrey, L. E.
Article Title: Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas
Abstract: Purpose: Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. Methods and Materials: After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab. Results: Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%. Discussion: Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma. © 2009 Elsevier Inc. All rights reserved.
Keywords: vasculotropin; adult; clinical article; controlled study; treatment response; aged; aged, 80 and over; disease-free survival; middle aged; vascular endothelial growth factor a; fatigue; neutropenia; bevacizumab; drug efficacy; drug safety; drug withdrawal; gastrointestinal hemorrhage; hypertension; cancer radiotherapy; radiation dose; combined modality therapy; brain neoplasms; progression free survival; multiple cycle treatment; neoplasm recurrence, local; anemia; radiation; bleeding; leukopenia; thrombocytopenia; radiotherapy; monoclonal antibodies; lymphocytopenia; hyponatremia; antibodies, monoclonal; physical therapy; tumor recurrence; glioblastoma; radiosurgery; irradiation; intestine perforation; tumor growth; disease control; dose fractionation; angiogenesis inhibitors; wound healing impairment; astrocytoma; wound dehiscence; anti-angiogenesis; intensity-modulated radiation therapy; malignant gliomas; central nervous system bleeding; hypofractionated stereotactic radiotherapy; optic chiasm; perfusion weighted imaging; stereotactic procedure; tumor bleeding
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 75
Issue: 1
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2009-09-01
Start Page: 156
End Page: 163
Language: English
DOI: 10.1016/j.ijrobp.2008.10.043
PUBMED: 19167838
PROVIDER: scopus
PMCID: PMC3659401
DOI/URL:
Notes: --- - "Cited By (since 1996): 20" - "Export Date: 30 November 2010" - "CODEN: IOBPD" - "Source: Scopus"
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MSK Authors
  1. Nimish Arun Mohile
    13 Mohile
  2. Yoshiya Yamada
    376 Yamada
  3. Philip H Gutin
    160 Gutin
  4. Jenghwa Chang
    63 Chang
  5. Fabio M Iwamoto
    36 Iwamoto
  6. Bob L Hou
    22 Hou
  7. Kathryn Beal
    167 Beal
  8. Sasan Karimi
    98 Karimi
  9. Lauren E Abrey
    275 Abrey
  10. Jerry C Chang
    1 Chang