2064 Background: Liposomal cytarabine (DepoCyt) is a sustained-release intrathecal (IT) preparation of cytarabine, formulated by encapsulating the drug in spherical aqueous chambers within a lipid matrix. While proven effective in lymphomatous meningitis, this drug has shown some activity in medulloblastoma (MB) with spinal metastases in limited pediatric phase I study. Methods: We reviewed all patients at our institution treated with liposomal cytarabine for primary central nervous system (CNS) embryonal tumors-MB, primitive neuroectodermal tumor (PNET), and atypical teratoid rhabdoid tumor (ATRT). Results: A cohort of 17 patients were treated with liposomal cytarabine at diagnosis of CNS embryonal tumor (2 PNET, 3 ATRT) or relapse (12 MB [7 average-risk, 5 high-risk]); nine had leptomeningeal metastases. Drug was dosed at 2 mg/kg up to 50, every 2 weeks to monthly, along with dexamethasone. Concurrent systemic chemotherapy was given in 16 patients. Median age at first dose was 10.8 years (range 0.9 to 27.9 years). A total of 102 doses were administered (lumbar IT 76, Ommaya intraventricular 36) with a mean of six treatments (range 1–16). Only three administrations were associated with adverse effects of arachnoiditis or headache; no dose reductions were required. Median overall survival from relapse was 11.8 months. All six evaluable patients with malignant cerebrospinal fluid (CSF) cytology and treated with at least two doses cleared their spinal fluid (mean 3 doses, range 1–5). No patient developed malignant CSF cytology while receiving liposomal cytarabine. Ten patients developed progressive disease and died, with only one later recurrence in the spinal fluid. Seven patients remain alive (4 initial and 3 relapse) with five in continuous complete remission (2 ATRT) for a median 13.7 months from first liposomal cytarabine. Conclusions: Liposomal cytarabine was well tolerated and easily administered. All patients with neoplastic meningitis cleared malignant cells from their spinal fluid after treatment with IT liposomal cytarabine and systemic chemotherapy. One-third of our cohort remains in remission from otherwise fatal diagnoses. Our findings warrant a phase II trial of liposomal cytarabine in newly diagnosed or recurrent CNS embryonal tumors. [Table: see text]
EAPH-05. MOLECULAR PROFILING AND IDENTIFICATION OF TARGETED THERAPIES FOR CHILDREN AND YOUNG ADULTS WITH PRIMARY CENTRAL NERVOUS SYSTEM TUMOURS IN THE UNITED KINGDOM
