The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma

Abstract

BackgroundBrainstem gliomas (BSG) are relatively rare tumors of which recurrent pediatric diffuse intrinsic pontine gliomas (RPDIPG) comprise a distinct group. Numerous trials have been conducted on RPDIPG, none of which have resulted in identifying any proven pharmacological treatment benefit. This study included 40 patients diagnosed with different types of BSG, but it was decided to describe first the encouraging results in the most challenging group of RPDIPG.Materials and methodsThis single-arm phase II study evaluated the efficacy and safety of the combination of antineoplastons A10 and AS2-1 (ANP) in patients with RPDIPG. Seventeen patients (median age 8.8 years) were enrolled, and all were diagnosed with RPDIPG. ANP was administered intravenously daily. Efficacy analyses were conducted in this group of patients.ResultsIn this group, complete responses were observed in 6 % of patients, partial responses in 23.5 %, and stable disease in 11.8 %. Six-month progression-free survival was 35.3 %. One-year overall survival was 29.4 %, 2 years 11.8 %, and 5, 10, and 15 years 5.9 %. One patient with DIPG is alive over 15 years post-treatment. Grade 3 and higher toxicities including hypokalemia and fatigue occurred in 6 %, hypernatremia in 18 %, fatigue and urinary incontinence in 6 %, and somnolence in 12 %. In a single patient, grade 4 hypernatremia occurred when he was on mechanical ventilation. He was disconnected from the ventilator and died from brain tumor according to the attending physician. Responding patients experienced improved quality of life.ConclusionThe results suggest that ANP shows efficacy and acceptable tolerability profile in patients with RPDIPG.

A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Primary Brain Tumors—Final Report (Protocol BT-09)

“…The responses observed in other high-grade brain tumors are interesting, but the population of patients is too small to draw conclusions. The additional studies provided data on the efficacy of ANP in GBM, PNET and BSG [9]- [17] [37].…”

Complete Response and Long-Term Survival (>20 Years) of a Child with Tectal Glioma: A Case Report

“…This report suggests that it is possible to obtain long-term overall survival in patients suffering from tectal glioma with an aggressive course of the disease. The results of phase II studies of ANP are described in a number of articles [8,9,10]. …”

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Brain Tumors. Final Report (Protocol BT-10)

“…This paper discusses the results of a second study conducted according to Protocol BT-10, which was designed to provide a preliminary evaluation of the results of ANP therapy in newly-diagnosed and recurrent high-grade and low-grade pediatric brain tumors. Subsequent studies concentrated on different subgroups of pediatric brain tumors including brainstem glioma (BSG), LGA, optic pathway glioma (OPG), recurrent primitive neuroectodermal tumor (PNET), atypical teratoid/rhabdoid tumor (AT/RT), ependymoma, choroid plexus carcinoma, and craniopharyngioma (CP) [9]- [17]. The interim results on some of these trials have been published [6]- [17].…”