Erlotinib therapy for central nervous system hemangioblastomatosis associated with von Hippel-Lindau disease: a case report.

There is a need for effective systemic therapy for central nervous system (CNS) hemangioblastomas (HBs). We report a case of erlotinib therapy for CNS HBs in a patient with von Hippel-Lindau disease, in whom the HBs were associated with diffuse leptomeningeal seeding. We provide the first report of paired serum and cerebrospinal fluid (CSF) levels of erlotinib while on standard dosing. The patient exhibited neurologic and imaging signs of recurrent CNS HBs and progressive leptomeningeal metastasis following surgery, radiation, and stereotactic radiosurgery. The patient was treated with erlotinib 150 mg daily. The patient achieved a minor response to erlotinib therapy, including clinical improvement, reduction in size of two enhancing brain lesions (one of which, however, proved at autopsy to be radiation necrosis) and stabilization of leptomeningeal enhancement. In addition, the CSF white count improved. The duration of response was 9 months. The median plasma and CSF levels of erlotinib while on treatment were 1146.06 and 247.83 ng/ml, respectively (CSF 21.6% of plasma). Erlotinib may have antitumor activity in CNS HBs.