Randomized double-blind placebo-controlled trial of bevacizumab therapy for
radiation necrosis of the central nervous system.
Author(s): Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele BN, Grewal J, Prabhu S,
Loghin M, Gilbert MR, Jackson EF.
Affiliation(s): Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center,
Houston, TX 77230-1402, USA. vlevin49@comcast.net
Publication date & source: 2011, Int J Radiat Oncol Biol Phys. , 79(5):1487-95
PURPOSE: To conduct a controlled trial of bevacizumab for the treatment of
symptomatic radiation necrosis of the brain.
METHODS AND MATERIALS: A total of 14 patients were entered into a
placebo-controlled randomized double-blind study of bevacizumab for the treatment
of central nervous system radiation necrosis. All patients were required to have
radiographic or biopsy proof of central nervous system radiation necrosis and
progressive neurologic symptoms or signs. Eligible patients had undergone
irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma.
Patients were randomized to receive intravenous saline or bevacizumab at 3-week
intervals. The magnetic resonance imaging findings 3 weeks after the second
treatment and clinical signs and symptoms defined the response or progression.
RESULTS: The volumes of necrosis estimated on T(2)-weighted fluid-attenuated
inversion recovery and T(1)-weighted gadolinium-enhanced magnetic resonance
imaging scans demonstrated that although no patient receiving placebo responded
(0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7
crossover) with decreases in T(2)-weighted fluid-attenuated inversion recovery
and T(1)-weighted gadolinium-enhanced volumes and a decrease in endothelial
transfer constant. All bevacizumab-treated patients-and none of the
placebo-treated patients-showed improvement in neurologic symptoms or signs. At a
median of 10 months after the last dose of bevacizumab in patients receiving all
four study doses, only 2 patients had experienced a recurrence of magnetic
resonance imaging changes consistent with progressive radiation necrosis; one
patient received a single additional dose of bevacizumab and the other patient
received two doses.
CONCLUSION: The Class I evidence of bevacizumab efficacy from the present study
in the treatment of central nervous system radiation necrosis justifies
consideration of this treatment option for people with radiation necrosis
secondary to the treatment of head-and-neck cancer and brain cancer.
Erratum in
Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):6. Grewal, Jai [added].
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