Hearing improvement after bevacizumab in patients with neurofibromatosis type 2.

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N Engl J Med. 2009 Jul 23;361(4):358-67. Epub 2009 Jul 8.

Hearing improvement after bevacizumab in patients with neurofibromatosis type 2.
 
Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, Halpin C, Padera TP, Tyrrell A, Sorensen AG, Jain RK, di Tomaso E.

Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.

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. 2009 Massachusetts Medical Society