Explore this issue:May 2013
ORLANDO—The Combined Otolaryngology Spring Meetings, held here April 10–14, featured the annual meetings of several otolaryngology organizations, covering topics ranging across ear, nose and throat care. Here are a few highlights from the programs of some of these organizations.
Progress Treating Neurofibromatosis Type 2
American Neurotology Society
Several trials are ongoing and showing some promise in the treatment of neurofibromatosis type 2 (NF2), said Bradley Welling, MD, PhD, chair of otolaryngology-head and neck surgery at Ohio State University’s College of Medicine in Columbus, during his William F. House Lecture at the Annual Spring Meeting of the American Neurotology Society.
Lapatinib, an erbB2/EGF-inhibitor, is being studied in a phase 0 trial, with enrollment nearing a close. Patients will be treated 10 days pre-operatively, and then the tumor will be removed, with the drug concentration and molecular target assessed. That trial is being led by Johns Hopkins, along with Ohio State and other centers.
An earlier phase 2 study found a 15 percent reduction in tumor volume in four of 17 patients and a 10-decibel improvement in hearing in four of 13 (Neuro Oncol. 2012;14:1163-1170).
In the first study of the VEGF-inhibitor bevacizumab in NF2, 13 of 23 showed a hearing response, some with “quite remarkable” improvement, Dr. Welling said (Otol Neurotol. 2012;33:1046-1052). Two Phase 2 trials, which will assess hearing response and radiographic change, are getting underway, he said.
At Ohio State, a phase 1 study of the HDAC-inhibitor AR42 will assess safety. While the study was originally meant to include only liquid tumors, solid tumors, including NF2 patients, have been added. Eighteen patients, five with NF2-related tumors, have been enrolled in the dose-escalation study.
In all, eight drugs are now in trials for NF2, and are critically needed considering that the disorder has a 20-year survival rate of just 38 percent and causes deafness, facial paralysis and stroke. For now, treatment has to take into account the seriousness of the tumors found, along with the patient’s willingness to accept the risk of clinical trials.
Beyond that, the research has some other challenges, Dr. Welling said. He emphasized that the drugs will have to be well-tolerated because they may need to be taken for a lifetime. “How do we define success?” he said. “Certainly, I think if we stop tumor growth, for most of us, we consider that successful. We don’t necessarily have to see the tumor regress. Do we decide based on the effect of the growth on the target? And how sustainable is the treatment?”