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Clinical Trial
. 2014 Dec;30(12):2051-61.
doi: 10.1007/s00381-014-2401-z. Epub 2014 Apr 10.

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

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Free PMC article
Clinical Trial

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

Stanislaw R Burzynski et al. Childs Nerv Syst. .
Free PMC article

Abstract

Background: Brainstem 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 methods: This 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.

Results: In 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.

Conclusion: The results suggest that ANP shows efficacy and acceptable tolerability profile in patients with RPDIPG.

Figures

Fig. 1
Fig. 1
Proposed mechanism of action of antineoplastons A10 and AS2-1. The ingredients of antineoplastons A10 and AS2-1, PN and PG, affect signal transmission through AKT and RAS pathways, promote apoptosis, and interrupt cell cycle progression at G1/S and G2/M checkpoints
Fig. 2
Fig. 2
DIPG in a 10-year-old male (case 8) which recurred two times after partial surgical resection. MRI of the head: 1—T1 nonenhanced, 2—contrast-enhanced, 3—T2W, and 4—FLAIR images. PR was documented by the MRI and CR was established by the normalization of the follow-up PET scans. Arrows indicate tumors
Fig. 3
Fig. 3
DIPG in a 7-year-old female (case 9) which recurred after radiation therapy and chemotherapy with etoposide. MRI of the head: 1—T1 nonenhanced, 2—contrast-enhanced, and 3—T2W images. MRI documented PR. Arrows indicate tumors
Fig. 4
Fig. 4
The Kaplan-Meier survival curves from the start of treatment for recurrent pediatric DIPG

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