Minimal treatment options exist for advanced, inoperable neurofibromatosis type 2 (NF2), which is a rare tumor-prone disorder. NF2 results from a mutation in the NF2 tumor-suppressor gene on chromosome 22q12. NF2 is genetically and phenotypically distinguished from neurofibromatosis type 1, which results from a mutation in the NF1 tumor-suppressor gene located on chromosome 17q11.1,2 Clinically, NF2 is inherited in an autosomal dominant fashion and manifests through the appearance of bilateral acoustic neuromas (vestibular schwannomas), which lead to progressive hearing loss.3 Vestibular schwannomas and other lesions seen in patients with NF2 that arise progressively from other sites, such as meningiomas, spinal schwannomas, astrocytomas, ependymomas, rarely neurofibromas, and peripheral neuropathies, lead to profound morbidity in this debilitating disease.1,4 Few options are available to these patients outside of surgery, which is the mainstay of treatment for NF2-associated lesions, and, in some instances, radiation therapy.1,2 Despite our understanding of the underlying genetics and molecular pathophysiology of this disorder, patients become debilitated from tumor-related comorbidities. Recently, the anti–vascular endothelial growth factor (VEGF) antibody bevacizumab and erlotinib exhibited promising activity in pilot trials.5–8 Other than these two agents, no medical options are available for patients with NF2 with surgically unresectable disease. Because patients with NF2 harbor an aberration in a single gene, merlin, the protein product of which impacts multiple signals, including PI3-kinase/Akt, Raf/mitogen-activated protein/extracellular signal-regulated kinase, and mammalian target of rapamycin (mTOR), it is conceivable that one of the many agents that target these pathways that have already shown antitumor activity in malignancies will also cause the regression of NF2-related tumors.9–11
Because of its extreme rarity, conducting large clinical trials in NF2 is generally unfeasible.9 Therefore, we enrolled patients with NF2 onto various rationally targeted trials and sought response signals. We reviewed the records of consecutive patients with NF2 who were referred to the Clinical Center for Targeted Therapy (phase I Clinical Trials Program clinic) who were treated in more than one trial starting in January 2007 to December 2010. All trials were approved by the MD Anderson institutional review board, which also granted a waiver of informed consent and a waiver of authorization for this retrospective study. Patients were evaluated every 6 to 8 weeks for response by using RECIST with computed tomography and magnetic resonance imaging.