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Cancer Drug Shrinks Benign Tumors That Steal Hearing
Date:9/11/2009

Avastin returned sound to young adults with acoustic neuromas

FRIDAY, Sept. 11 (HealthDay News) -- Last year, Edith Garrett could no longer hear her mother's voice or the sound of a dog barking. She was 22.

Four years earlier, Garrett learned she had neurofibromatosis type 2 (NF2), a condition characterized by tumors in the nervous system. The benign tumors, acoustic neuromas, damaged the eighth cranial nerve in one ear.

The result: increasing hearing loss with no prospect of a cure.

Having already lost 92 percent of her hearing, the college student from Atlanta signed on for an experimental treatment -- a drug therapy federally approved to inhibit the formation of new blood vessels that feed tumors. The treatment involved infusions of bevacizumab, a drug marketed as Avastin that is sometimes used to treat advanced cancers.

Dr. Scott Plotkin, a neuro-oncologist at Massachusetts General Hospital in Boston, who led the trial, was looking for a medical option for his NF2 patients with acoustic neuromas. Not only do the tumors threaten hearing loss, but so can the current therapies, surgery and localized radiation.

Aware that his colleagues were having success with Avastin on certain other tumors, Plotkin had tried it on a 16-year-old boy who also had NF2. To his surprise, he succeeded in restoring the boy's hearing.

Although it was a long shot, he decided to try the therapy on Garrett, who was then relying on hearing aids.

While sitting in class one day, after receiving two infusions of Avastin two weeks apart, the young woman heard a distinct Southern accent for the first time in years. Later that day, she called home and could hear her mother's soothing voice. They were ecstatic.

Within three months of the start of treatment, Garrett's tumor shrank and her hearing improved dramatically -- from 8 percent to 98 percent.

Inspired by these two breakthroughs, Plotkin enlisted eight other young people with NF2 who developed the acoustic neuromas that threaten hearing. No longer candidates for surgery, they, too, were on the brink of deafness.

The therapy wasn't uniformly successful, but tumors shrank 20 percent or more in six patients, Plotkin reported last month in the New England Journal of Medicine. Four patients had their hearing restored, and none reported serious side effects.

This was the first successful trial of a medicine to reverse hearing loss and reduce tumor volume in NF2 patients, Plotkin wrote in the study. The drug's success opens the door to new treatments for these very complex cases, he said.

The disease, caused by a genetic mutation, shows symptoms by adolescence or young adulthood.

NF2 tumors appear to have a blood supply fueled by vascular endothelial growth factor (VEGF), a signaling protein involved with blood vessel formation. Avastin is one of several drugs that block production of the protein, apparently shrinking the tumor as a result.

More work needs to be done, but the researchers are encouraged, Plotkin said. How long patients must undergo the infusion treatment is still unknown. And whether they will require the high doses that patients with malignant tumors receive must also be determined.

"These patients are young, and we know that any treatment will be long-term," said Plotkin. The team is now testing lower doses, in the hope of minimizing any long-term side effects.

"This treatment is indeed a novel approach," said Dr. Bruce Korf, chair of the department of genetics at the University of Alabama in Birmingham and an expert on neurofibromatosis.

"There is enough encouraging evidence to lead to a larger study of this treatment for NF patients," added Korf. "It is really exciting, but will require a lot of follow-up research."

Emmanuelle di Tomaso, who did pioneering work with bevacizumab and tumors at Massachusetts General, is also enthusiastic. "We were all fascinated by what we were seeing in the patients," said study co-author Di Tomaso, who is now a biomarker project leader at Novartis Institute for BioMedical Research in Cambridge, Mass.

Garrett, meanwhile, graduated from college and went to graduate school to study mathematics. In September, she will begin teaching math at a school for the deaf and hearing-impaired in Georgia.

She doesn't know how long she can take the medicine, but Plotkin said he hopes to answer that question soon.

For now, she revels in hearing the everyday sounds that she lost for a while. "I got my life back," she said. "I am so lucky."

More information

Go to the National Library of Medicine for more on acoustic neuromas.



SOURCES: Scott Plotkin, M.D., clinical director, Neurofibromatosis Clinic, Massachusetts General Hospital, Boston; Bruce Korf, M.D., professor and chair, department of genetics, University of Alabama, Birmingham; Emmanuelle di Tomaso, Ph.D., biomarker project leader, Novartis Institute for BioMedical Research, Cambridge, Mass.; July 23, 2009, New England Journal of Medicine


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