Pharmacologic approaches to the treatment of meningeal malignancy

The meninges are a unique site of recurrence for certain malignancies because of the limited penetration of systemically administered cytotoxic drugs across the blood-brain barrier. While this phenomenon was first recognized in children with acute lymphoblastic leukemia, a similar pattern is also occurring in breast cancer, ovarian cancer, and small cell lung cancer. Recognition of the limitations of standard systemic antileukemic therapy for the treatment of meningeal disease led to the development of new therapeutic strategies targeted directly at the CNS. These include intralumbar therapy using methotrexate or cytarabine, intraventricular chemotherapy, and high-dose systemic drug administration. New agents showing promise are intrathecal diaziquone, 6-mercaptopurine, and mafosfamide.