Authors: Scott R Plotkin Chris Halpin Jaishri O Blakeley William H Slattery D Bradley Welling Susan M Chang Jay S Loeffler Gordon J Harris A Gregory Sorensen Michael J McKenna Fred G Barker
Publish Date: 2009/05/09
Volume: 93, Issue: 1, Pages: 61-77
Abstract
Neurofibromatosis type 2 NF2 is a tumor suppressor gene syndrome characterized by multiple schwannomas especially vestibular schwannomas VS and meningiomas Anticancer drug trials are now being explored but there are no standardized endpoints in NF2 We review the challenges of NF2 clinical trials and suggest possible response criteria for use in initial phase II studies We suggest two main response criteria in such trials Objective radiographic response is defined as a durable 20 or greater reduction in VS volume based on postcontrast T1weighted MRI images collected with 3 mm or finer cuts through the internal auditory canal Hearing response is defined as a statistically significant improvement in word recognition scores using 50word recorded lists in audiology A possible composite endpoint incorporating both radiographic response and hearing response is outlined We emphasize pitfalls in response assessment and suggest guidelines to minimize misinterpretations of response We also identify research goals in NF2 to facilitate future trial conduct such as identifying the expectations for time to tumor progression and time to measurable hearing loss in untreated NF2related VS and the relation of both endpoints to patient prognostic factors such as age baseline tumor volume and measures of disease severity These data would facilitate future use of endpoints based on stability of tumor size and hearing which might be more appropriate for testing certain drugs We encourage adoption of standardized endpoints early in the development of phase II trials for this population to facilitate comparison of results across trials of different agents
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