A Phase II study of antineoplastons A10 and AS2-1 in pediatric recurrent diffuse intrinsic pontine glioma

Stanislaw Burzynski 1 ,2, Tomasz Janicki1 ,2, Gregory Burzynski1 ,2, Ania Marszalek1
1Burzynski Clinic, Houston, TX, USA, 2Burzynski Research Institute, Houston, TX, USA


Brainstem gliomas (BSG) are rare tumors of which diffuse intrinsic pontine gliomas (DIPG) comprise a distinct group. Numerous trials have been conducted in DIPG without a proven pharmacological treatment benefit. Prior interim report on this phase II study of antineoplastons (ANP) A10 and AS2-1 provided data on 40 patients diagnosed with BSG.  This report is focused on final results of 17 out of 40 patients diagnosed with recurrent pediatric DIPG (RPDIPG). The median age in this group was 8.8 years (range 4.5-18.5), with 9 females and 8 males. Previous treatment included radiation therapy (RT) in 15 patients, chemotherapy in 11 patients and surgery in 2 patients. At least eight weeks elapsed from initiation of ANP and previous RT and six weeks from chemotherapy with nitrosoureas. ANP was administered daily through a subclavian venous catheter via infusion pump.  The median duration of treatment was 5.6 months.  The median of average dosages of A10 was 8.8 g/kg/d and 0.40 g/kg/d of AS2-1. Responses were assessed by MRI repeated every eight weeks.  In the RPDIPG group, a complete response (CR) was 6%, partial response (PR) 23.5%, and stable disease (SD) 23.5%. 6 month progression-free survival (PFS) was 35.3%. 1 year overall survival (OS) was 29.4%, 2 years 11.8%, and 5, 10 and 14 years 5.9%.  One patient has OS and PFS of 14 years from the treatment start. Grade 4 toxicities including hypernatremia, hypokalemia and fatigue occurred in less than 18% of patients. Grade 3 fatigue, somnolence, skin allergy and urinary incontinence occurred in 6-12 %. There were no chronic adverse events. Responding patients experienced improved quality of life. The results suggest that ANP shows efficacy and an acceptable tolerability in patients with RPDIPG.