MB-29: RECURRENT MEDULLOBLASTOMA AND ATYPICAL TERATOID RHABDOID TUMOR: PROLONGED SURVIVAL WITH AN ANTIANGIOGENIC COMBINATION THERAPY

Prognosis of patients with recurrent medulloblastoma and atypical teratoid rhabdoid tumor (ATRT) is dismal independent of type of conventional therapy used including high-dose chemotherapy with stem cell rescue. An alternative approach is an antiangiogenic combination therapy. From 11/2006-12/2015, 17 patients with recurrent medulloblastoma (11 first, 6 multiple recurrences) and eight with recurrent ATRT (5 first, 3 multiple) started treatment consisting of an antiangiogenic multidrug-regime including IV bevacizumab, oral thalidomide, celecoxib, fenofibrate, and etoposide alternating with cyclophosphamide, and augmented with intraventricular therapy (etoposide and liposomal cytarabine). Median age at start of antiangiogenic therapy was 10 (1-24) years for medulloblastoma and 4 (1-13) years for ATRT. As of 02/2016, 10/17 patients with medulloblastoma are alive, 7 in CR at a median of 36 (13-87) months, two are in PR 9 and 8 months after their last recurrence, and one is progressive. Six patients are off therapy for 69, 52, 50, 27, 6 and 5 months. 5-year-OS is 63 ± 15%. 3/8 patients with ATRT are in CR, one in PR. Follow-up since last recurrence is 62, 17, 15 and 5 months, three are off therapy for 42, 4 and 3 months. One medulloblastoma and one ATRT patient died of another cause in CR 23 and 54 months after their last recurrence. Therapy was generally well tolerated and toxicities were manageable. The proposed antiangiogenic regimen is currently being evaluated for medulloblastomas in an international phase II protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290). The same approach seems to be also efficacious in recurrent ATRTs.