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.
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