Safety Of Interventricular Methotrexate Administration Following Radiation In Pediatric Patients With Malignant Brain Tumors

Abstract BACKGROUND Methotrexate has been used for intrathecal administration in leukemia as well as embryonal CNS tumors in children. Concerns about neurologic side effects including leukoencephalopathy, demyelination, and seizures have limited the use of methotrexate following exposure to focal radiation. OBJECTIVE To evaluate and determine safety of Intraventricular administration of Methotrexate in pediatric patients with recurrent malignant brain tumors along with systemic Topotecan and Cyclophosphamide after exposure to prior radiation therapy. DESIGN/METHOD: Patients with recurrent cerebellar embryonal tumors after standard treatment that included radiation were enrolled on this IRB approved phase 2 study. An Ommaya reservoir was inserted in the lateral ventricle and used to administer 4 daily doses of methotrexate (2 mg/dose) along with (Topotecan [0.75mg/m2/day] and Cyclophosphamide [250 mg/m2/day]). A neurological evaluation was performed at baseline and daily during the intraventricular administration of the Methotrexate, this evaluation was repeated prior to each subsequent cycle and at completion of the protocol. RESULTS Three patients (age range 3–20) received 2–3 cycles of intra-Ommaya Methotrexate and Topotecan/Cyclophosphamide. No MRI demyelination or white matter changes were seen after completion of the intraventricular Methotrexate therapy. None of the patients enrolled on this trial had adverse effects related to the therapy regimen received. Clinical neurological status was unchanged during the entire course of the treatment and upon completion of the scheduled therapy. CONCLUSION Intraventricular administration of daily low dose Methotrexate is well tolerated in children with recurrent embryonal CNS tumors who had prior exposure to radiation.