In a paper to appear in the July 23 New England Journal of Medicine, which is receiving early online release, researchers from Massachusetts General Hospital (MGH), Boston, report that Avastin treatment successfully shrank characteristic tumors in a small group of NF2 patients, the first reported successful NF2 treatment not involving surgery or radiation, according to a statement released by the hospital.

Scott Plotkin, MD, PhD, Pappas Center for Neuro-Oncology in the MGH Cancer Center, and lead author of the NEJM paper said in the statement that this kind of treatment response is unprecedented. The study is the first to provide evidence that a drug can shrink vestibular schwannomas—benign tumors on the balance and hearing nerves—and the first to show that patients’ hearing can be improved, he added.

According to the stastement, NF2 is an inherited genetic disorder in which benign tumors develop throughout the nervous system. Vestibular schwannomas are the most common NF2-associated tumors, and although they grow slowly, they usually cause patients to lose all or most of their hearing by young adulthood or middle age. The tumors can be removed surgically or treated with radiation, but in patients with vestibular schwannomas on both sides, which is typical in NF2, such treatment usually leads to complete hearing loss. Growing vestibular schwannomas can also press on the brainstem, leading to headaches, difficulty swallowing, and other serious neurologic symptoms.

Since vestibular schwannomas are benign tumors, it was believed that they did not stimulate formation of new blood vessels as malignant tumors do, according to the statement, which notes: When the researchers studied tissue samples from NF2-related schwannomas, sporadic tumors not caused by NF2 and normal spinal nerves, they found evidence of excess blood vessel development and increased expression of angiogenesis-related molecules in both NF2-associated and sporadic vestibular schwannomas. With this suggestion that angiogenesis was involved in these tumors, members of the research team offered treatment with bevacizumab (Avastin), which is FDA-approved for treatment of several forms of cancer, to NF2 patients in danger of complete hearing loss or other significant neurological damage.

Among the first ten NF2 patients to receive Avastin, treatment led to tumor shrinkage in nine, and six had 20% or greater reduction in tumor size, says the statement. In those six patients, tumor shrinkage lasted from 11 to 16 months, longer than the four months typically seen in Avastin treatment of malignant brain tumors. Of seven patients who had started to lose their hearing before treatment, four experienced some hearing restoration—two returned to work or school as a result—improvement that has also lasted for up to 16 months. In one patient without significant tumor shrinkage or hearing improvement (he had lost all hearing prior to treatment), treatment alleviated headaches and nausea caused by brainstem compression, allowing him also to return to school.

Emmanuelle di Tomaso, PhD, the study’s senior author, formerly with the Steele Laboratory of Tumor Biology in the MGH Department of Radiation Oncology said in the statement that the study has opened a new approach to research and understanding of these tumors. There had been a dogma that these tumors do not produce edema and are not angiogenic, concepts that now need to be reevaluated, she added, noting further that the study also suggests that VEGF—the angiogenesis factor blocked by Avastin—may have a role in nerve physiology beyond the stimulation of blood vessel growth.

Plotkin further said that, based on the study’s results, the researchers have just opened the first formal clinical trial of a drug treatment for NF2. They are testing an exciting new, oral VEGF inhibitor that will be easier for patients to take—Avastin is administered intravenously—and may have fewer side effects, he added.

Plotkin is an assistant professor of neurology at Harvard Medical School (HMS). Formerly an assistant professor of radiation oncology at HMS, di Tomaso recently joined the Novartis Institutes for BioMedical Research. Additional co-authors of the NEJM report are Anat Stemmer-Rachamimov, MD, MGH pathology; Fred Barker, MD, MGH neurosurgery; Timothy Padera, PhD, Alex Tyrrell, PhD, and Rakesh Jain, PhD, MGH radiation oncology; Gregory Sorensen, MD, MGH radiology, and Chris Halpin, PhD, Massachusetts Eye and Ear Infirmary.

The study was supported by the HMS Center for Neurofibromatosis and Allied Disorders, Neurofibromatosis Inc New England, Children’s Tumor Foundation, the Department of Defense, the National Institutes of Health, and the MGH Executive Committee on Research. No support was provided by Genentech, which produces and markets bevacizumab under the brand name Avastin.

[Source: Massachusetts General Hospital]