Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas.
OBJECTIVE
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
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%.


CONCLUSIONS
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.
Gutin
Philip H
PH
Department of Neurosurgery, The Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. gutinp@mskcc.org
Iwamoto
Fabio M
FM
Beal
Kathryn
K
Mohile
Nimish A
NA
Karimi
Sasan
S
Hou
Bob L
BL
Lymberis
Stella
S
Yamada
Yoshiya
Y
Chang
Jenghwa
J
Abrey
Lauren E
LE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001254:Astrocytoma / Q000188:drug therapy / Q000601:surgery; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000601:surgery; D003131:Combined Modality Therapy / Q000009:adverse effects; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000601:surgery; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab