Hearing improvement after bevacizumab in patients with neurofibromatosis type 2.

Abstract

BACKGROUND:

Profound hearing loss is a serious complication of neurofibromatosis type 2, a genetic condition associated with bilateral vestibular schwannomas, benign tumors that arise from the eighth cranial nerve. There is no medical treatment for such tumors.

METHODS:

We determined the expression pattern of vascular endothelial growth factor (VEGF) and three of its receptors, VEGFR-2, neuropilin-1, and neuropilin-2, in paraffin-embedded samples from 21 vestibular schwannomas associated with neurofibromatosis type 2 and from 22 sporadic schwannomas. Ten consecutive patients with neurofibromatosis type 2 and progressive vestibular schwannomas who were not candidates for standard treatment were treated with bevacizumab, an anti-VEGF monoclonal antibody. An imaging response was defined as a decrease of at least 20% in tumor volume, as compared with baseline. A hearing response was defined as a significant increase in the word-recognition score, as compared with baseline.

RESULTS:

VEGF was expressed in 100% of vestibular schwannomas and VEGFR-2 in 32% of tumor vessels on immunohistochemical analysis. Before treatment, the median annual volumetric growth rate for 10 index tumors was 62%. After bevacizumab treatment in the 10 patients, tumors shrank in 9 patients, and 6 patients had an imaging response, which was maintained in 4 patients during 11 to 16 months of follow-up. The median best response to treatment was a volumetric reduction of 26%. Three patients were not eligible for a hearing response; of the remaining seven patients, four had a hearing response, two had stable hearing, and one had progressive hearing loss. There were 21 adverse events of grade 1 or 2.

CONCLUSIONS:

VEGF blockade with bevacizumab improved hearing in some, but not all, patients with neurofibromatosis type 2 and was associated with a reduction in the volume of most growing vestibular schwannomas.

• Authors: Scott R Plotkin, Anat O Stemmer-Rachamimov, Fred G Barker 2nd, Chris Halpin, Timothy P Padera, Alex Tyrrell, A Gregory Sorensen, Rakesh K Jain, Emmanuelle di Tomaso
• Journal: The New England journal of medicine (N Engl J Med) Vol. 361 Issue 4 Pg. 358-67 (Jul 23 2009) ISSN: 1533-4406 [Electronic] United States
• PMID: 19587327 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Massachusetts Medical Society

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Neuropilin-2
• Vascular Endothelial Growth Factor A
• Neuropilin-1
• Bevacizumab
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Adolescent
• Adult
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Female
• Hearing Loss (drug therapy, etiology)
• Humans
• Male
• Middle Aged
• Neurofibromatosis 2 (complications)
• Neuroma, Acoustic (complications, drug therapy, metabolism)
• Neuropilin-1 (metabolism)
• Neuropilin-2 (metabolism)
• Retrospective Studies
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)
• Young Adult