Neurofibromatosis type 2 (NF2) is a rare autosomal dominant genetic disorder with an
      incidence of approximately 1/40,000. The most common tumor type in NF2 is vestibular
      schwannoma and the majority of NF2 patients develop progressive hearing loss in adolescence
      or young adulthood due to bilateral vestibular schwannoma (VS). In addition to hearing loss,
      VS can cause significant morbidity, and in some cases mortality, due to brain stem
      compression.

      Currently, the only accepted modality for treatment of VS in patients with NF2 is surgical
      resection. Although surgical resection is effective at tumor reduction, it is often
      associated with morbid complications such as hearing loss, facial palsy, CSF leaks, chronic
      headache and infection. In addition, the tumors often recur after surgery. Radiation therapy
      (RT) has been proposed as an alternative, however, its safety in the NF2 population has not
      been established and there is concern about long term efficacy. For a distinct population of
      NF2 patients, surgery and RT at not feasible and no additional therapy is currently
      available. Hence, a systemic therapy is needed.

      Sporadic VS are common with roughly 3,000 new cases per year in the United States and a
      growing incidence in recent years. These tumors cause unilateral hearing loss, tinnitus, and
      vertigo. The primary treatment modality for these tumors is surgical resection or
      radiosurgery. Surgery is associated with the same complications listed above for NF2-related
      VS. Hence, RT is often offered in place of surgery. Although considered safe in sporadic VS,
      it may not have good long term efficacy and may complicate future procedures. Again, a
      systemic therapy that could control tumor progression obviating the need for an invasive
      procedure is needed.

      As the understanding of tumor molecular biology continues to advance, there are an increasing
      number of attractive targets for VS growth inhibition. EGFR and ErbB2 have been identified as
      important targets for VS. In a study of 21 sporadic and 17 NF2-related VS samples, both EGFR
      and ErbB2 were found to be upregulated in the majority of tumors. In addition, an anti-ErbB2
      monoclonal antibody reduced schwannoma cell proliferation in vitro. Collectively, this data
      suggests that abnormal signaling via EGFR and ErbB2 is a major contributor to tumor growth
      and progression in both sporadic and NF2-related VS, and that inhibition of this signaling
      pathway can result in decreased tumor growth. Although agents targeting these pathways are
      commercially available, there is little pre-clinical data to assist in prioritizing which
      agents to advance to clinical trials. Given the relative rarity of the disorder and the
      enormous patient, financial and time commitments an efficacy study requires, there is a need
      to carefully select agents for testing that have the best chance of success.

      In this trial, we propose to assess the delivery of lapatinib, a commercially available
      inhibitor of ErbB2 and EGFR, to VS via tissue sampling at the time of clinically indicated
      surgery. Demonstrating that lapatinib reaches meaningful intratumoral concentrations is
      important data to recommend this drug above other small molecule inhibitors for efficacy
      trials for VS. The primary objective is to determine the steady state concentration of
      lapatinib in VS in patients with NF2 and in patients with sporadic VS. Patient who are
      planning to have surgical resection of their tumor for clinical indications will be given
      lapatinib for 15 days prior to resection. At the time of resection, VS tissue will be
      assessed for drug concentration and molecular markers of drug activity.

      Demonstrating that lapatinib reaches meaningful concentrations within VS would support
      selecting this agent for investigation in efficacy studies for VS, and tissue-based molecular
      studies will provide corollary information about the behavior of VS in general and about
      lapatinib specifically in VS tissue. This may further our understanding of the
      pathophysiology of VS, the similarities and differences between NF2-related and sporadic VS,
      and inform the design of subsequent efficacy trials.