Hearing improvement after bevacizumab in patients with neurofibromatosis type 2.
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.
Plotkin
Scott R
SR
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA. splotkin@partners.org
Stemmer-Rachamimov
Anat O
AO
Barker
Fred G
FG
Halpin
Chris
C
Padera
Timothy P
TP
Tyrrell
Alex
A
Sorensen
A Gregory
AG
Jain
Rakesh K
RK
di Tomaso
Emmanuelle
E
D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005260:Female; D034381:Hearing Loss / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016518:Neurofibromatosis 2 / Q000150:complications*; D009464:Neuroma, Acoustic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism; D039943:Neuropilin-2 / Q000378:metabolism; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039943:Neuropilin-2; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D000068258:Bevacizumab; D040301:Vascular Endothelial Growth Factor Receptor-2