In a small clinical study with an anticancer drug that can halt tumor and blood vessel growth, researchers at Johns Hopkins Medicine, the National Institutes of Health, and Massachusetts General Hospital, found that a handful of people with neurofibromatosis type 2 (NF2) and hearing loss had restoration of hearing. Results of the collaborative study were described in an article that ran in the March 14, 2016 edition of the Journal of Clinical Oncology.
An estimated one in 25,000 people is born with NF2, a hereditary tumor syndrome in which virtually everyone progresses to deafness because of vestibular schwannomas—tumors growing on the auditory nerves. The tumors arise from the Schwann cells that support and insulate nerves. These tumors also cause balance problems and brain stem compression.
“Our study shows that the hearing loss suffered by at least a subset of these patients isn’t permanent and that there is hope of reversing it,” said Jaishri Blakeley, MD, director of the Johns Hopkins Comprehensive Neurofibromatosis Center and associate professor of neurology, neurosurgery and oncology at the Johns Hopkins University School of Medicine. “We made life-changing hearing restoration our priority measure of success with this trial rather than relying on outcomes that may not affect a patient’s life, such as change in tumor size.”
Vestibular schwannomas, or tumors, produce unexpectedly high levels of a protein called VEGF that promotes blood vessel growth, which feeds tumors. Bevacizumab reduces VEGF levels in certain cancers, as well as in a form of macular degeneration, a blinding eye condition. Because of the anticancer drug’s well-documented effects, Blakeley and her colleagues thought the drug might shrink the tumors and improve hearing in patients with NF2.
For the study, the investigators treated 14 patients—four males and 10 females, aged 14 to 79—with NF2 and progressive hearing loss. Each got 7.5 milligrams per kilogram body weight of bevacizumab intravenously every three weeks for 48 weeks, followed by 24 weeks of observation—a dose lower than what is given to cancer patients.
Three patients experienced clinically important adverse events most likely due to the treatment: high blood pressure in two of them, and excessive bruising and bleeding in a third. All patients underwent hearing evaluations at the start of the trial, during, and at the end of study. The test asked patients to repeat back 100 one-syllable words played through headphones in a quiet room. Word recognition scores varied from 0% if no words were correctly identified to 100% if all words were correctly identified. Five patients (36%) achieved sustained hearing improvement with the treatment, and 12 patients transitioned from non-serviceable to serviceable hearing in the affected ear.
None of the patients experienced further hearing loss during the study, even though all patients had progressive hearing loss at the start of the study as a requirement for enrolling. All patients stopped bevacizumab treatment after 12 months to assess how long the hearing improvement lasted. Five of nine with improved hearing maintained this improvement for six months after the drug was stopped.
Dr Blakely reports that the trial results, although limited by the small number of patients, suggest that patients may not need to get doses of the drug as frequently as may be required for cancer and also may be able to take breaks in treatment. This may help reduce the frequency of negative side effects and control long-term healthcare costs.
To measure changes in the size of their tumors, patients underwent MRI scans of the brain before, during, and after treatment. Six patients (43%) showed a reduction in the size of their vestibular schwannoma tumors by more than 20%, though reduced tumor size did not correlate with hearing improvement in the study.
The researchers are exploring certain biomarkers indicating a drug response that could be used in future trials to better select patients that respond to the treatment. Further clinical trials are needed to confirm these results.
Source: Johns Hopkins Medicine
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