MBCL-27. RESPONSE OF RECURRENT MALIGNANT CHILDHOOD CNS TUMORS TO A MEMMAT BASED METRONOMIC ANTIANGIOGENIC COMBINATION THERAPY VARIES DEPENDENT ON TUMOR TYPE: EXPERIENCE IN 71 PATIENTS

Abstract Patients with recurrent malignant CNS tumors have a poor prognosis irrespective of salvage therapy applied. We used a metronomic antiangiogenic combination therapy and report on the response of individual tumor types to this approach. Since 2006, 81 patients with various recurrent malignant brain tumors started treatment with an antiangiogenic multidrug-regimen at the Medical University of Vienna. Therapy consisted of daily oral thalidomide, fenofibrate, celecoxib, and 21-day cycles of low dose oral etoposide alternating with cyclophosphamide augmented with IV bevacizumab and intraventricular therapy (etoposide and liposomal cytarabine). Excluding the 10 patients with recurrent medulloblastoma treated in the formal international protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290), 71 patients were treated according to the same strategy “off trial”. Diagnoses were medulloblastoma (n=20), atypical teratoid rhabdoid tumor (ATRT) (n=11), ependymoma (n=9), high grade glioma/diffuse intrinsic pontine glioma (HGG/DIPG) (n=9), and various other entities in the remaining patients. As of the end of 2017, 3-year and 5-year OS for the 20 patients with recurrent medulloblastoma was 64.2 ± 10.9% and for the 11 patients with recurrent ATRT 45.7 ± 16.6% and 30.5 ± 16.7%, respectively. Remission could be maintained after discontinuation of treatment in a certain percentage of patients with medulloblastoma, ATRT and ependymoma. Patients with HGG and DIPG did not respond to this approach. The proposed antiangiogenic regimen seems most promising in medulloblastoma and ATRT and possibly also ependymoma. In a number of other tumor entities time to progression could be prolonged while maintaining good quality of life.