EPT-22TREATMENT OF CHILDREN WITH PRIMARY CNS TUMORS AND LEPTOMENINGEAL, DISSEMINATED AND/OR MULTICENTRIC DISEASE IN PHASE II STUDIES WITH ANTINEOPLASTONS A10 AND AS2-1

Abstract

It is estimated that as many as 30% of patients with primary CNS tumors have leptomeningeal, disseminated, and/or multicentric disease (LDM). LDM patients respond poorly to conventional therapy. Fifty‐seven children with LDM (median age of 7.1 years) were treated in multiple phase II clinical studies of high‐and low‐grade primary CNS tumors with antineoplastons A10 and AS2‐1 (ANP). Their inclusion in this analysis was based on MRI imaging. GBM patients were excluded. The patients received ANP 6 times daily; A10: 8.77 g/kg/d; AS2‐1: 0.35 g/kg/d. The response to ANP was monitored by MRIs every 8 weeks. Patients evaluable for efficacy (N = 40) received 12 or more weeks of ANP or developed progressive disease (PD) before 12 weeks. Ten patients (17.5%) achieved an objective response (OR), 6 (10.5%) had a complete response (CR) and 4 (7%) had a partial response (PR). Stable disease (SD) was maintained in 7 patients (12%) and PD developed in 23 patients (40%). Survival analysis of the 57 children showed 2‐and 5‐year overall survival (OS) of 28% while 10‐and 15‐year OS was 26%. One of the children achieving an OR had atypical teratoid/rhabdoid tumor (AT/RT) while nine had low‐grade gliomas (LGGs). Grade 3 and 4 toxicities included hypokalemia (14.0%); fatigue, anemia, hypernatremia and leukopenia (3.5% each); diarrhea, hypertension, joint pain, thrombocytopenia, and somnolence (1.8% each). These preliminary Results suggest the need for a single‐arm, phase II study of ANP in children with LDM.