ANGI-10. METRONOMIC 5 DRUG ANTI-ANGIOGENESIS THERAPY FOR RECURRENT EPENDYMOMA

Abstract

Abstract Low dose continuous (metronomic) anti-angiogenesis therapy is a treatment regimen currently under investigation for chemo-refractory tumors to target tumor vasculature. This effect has been shown to improve survival in primary brain tumors such as medulloblastoma. The Dana Farber Antiangiogenic Chemotherapy Phase II Trial and MEMMAT trial are investigations into outcomes of metronomic anti-angiogenesis therapy for children with recurrent ependymoma, among other primary brain tumors. We retrospectively report 9 pediatric patients diagnosed between the ages of 1 and 8 with surgery and radiation refractory posterior fossa ependymoma that were treated with 5 drug metronomic anti-angiogenesis therapy including celecoxib, thalidomide, fenofibrate, and alternating low dose etoposide and cyclophosphamide. For one patient, we added bevacizumab every other week. 7 patients had anaplastic presentation of ependymoma. All patients either had gross total resection or multiple subtotal resections. Tumor markers include GFAP, S100, EMA, OLIG 2, CD99, and Ki-67. Side effects were primarily hematologic but also included muscle pain, constipation, and dizziness, however treatment was tolerated well overall. The primary reason for stopping treatment early was progression of disease, no patients stopped therapy for side effects. There was no change in response to therapy based on tumor markers found. 2-year survival was 78% and 2-year progression free survival was 56%. 3/9 patients have no recurrent disease, two of these patients had anaplastic ependymoma and 1 presented with metastatic disease to the spine. We show improved outcomes with a minimal side effect profile for metronomic anti-angiogenesis therapy in pediatric patients with recurrent ependymoma refractory to surgical and radiation therapy.