A modified multi-drug metronomic antiangiogenic approach in recurrent pediatric embryonal central nervous system tumors: an institutional experience

Abstract Background Approximately one third of pediatric patients with embryonal tumors of the central nervous system will experience a recurrence, with poor prognosis. Patients with recurrent or progressive disease may be treated with multi-drug metronomic antiangiogenic approaches. Methods We performed a retrospective review of 13 patients treated at a single institution from 2010-2023 using a multimodal metronomic antiangiogenic regimen which includes oral thalidomide, celecoxib and fenofibrate, and alternating etoposide/cyclophosphamide, intravenous bevacizumab, and alternating intraventricular etoposide, cytarabine, and topotecan. Results Toxicities included myelosuppression with at least one grade 3 hematologic toxicity in 11/12 (92%) patients. Other toxicities included infection, neurologic (cerebritis, irritability), hepatic (transaminitis), and a secondary leukemia. Seven patients required one or more drugs to be held or modified due to toxicity. The overall response rate was 69.2% (95% confidence interval (CI): 38.6%-90.9%) with median time to best response for patients who achieved CR or PR of 5 months. The median event-free survival (EFS) and overall survival (OS) time was 6 months (range: 1-21 months) and 15 months (range: 1.1-42.6 months), respectively. The 12-months EFS was 46.1% (95% CI: 19.2%-69.6%) with 12-months OS 83.9% (95% CI: 49.4%-95.7%). Conclusion Metronomic multi-drug approaches combining oral, intravenous and intraventricular/intrathecal therapy were generally well tolerated and provided a survival benefit.