TITLE:
A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Recurrent, Refractory or Progressive Primary Brain Tumors—Final Report (Protocol BT-22)
AUTHORS:
Stanislaw R. Burzynski, Tomasz J. Janicki, Gregory S. Burzynski, Ania Marszalek, Sheldon Brookman
KEYWORDS:
Anaplastic Astrocytoma, Antineoplastons A10 and AS2-1, Brainstem Glioma, Diffuse Intrinsic Pontine Glioma (DIPG), Gliosarcoma, Phase II Clinical Trial, Recurrent Glioma
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.10,
September
10,
2014
ABSTRACT: Primary malignant brain
tumors are a leading cause of cancer-related death in children. This Phase II
study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP)
in children who developed progression during standard treatment. A total of 43
children were recruited to the study, but only 41 met eligibility criteria.
There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic
astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three
supertentorial primitive neuroectodermal tumors (sPNET), three cases of
medulloblastoma and one case each of anaplastic ependymoma (AE), atypical
teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD).
ANP was administered intravenously daily every four hours (median dose of A10
8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was
documented, and then a further eight months. All enrolled patients were
included in safety, but only eligible patients in the efficacy evaluation. A
total of 12.2% of patients obtained OR; 2.4% complete response (CR) and 9.8%
partial response (PR). Stable disease (SD) was determined in 17.1% and
progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable
(NE) cases due to premature discontinuation. Out of five OR cases, four
patients were diagnosed with recurrent DIPG and one with recurrent AA. Median
progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8
months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five,
and ten years. The longest survivor is a patient diagnosed with DIPG and
gliosarcoma who remains alive more than 15 years. A group of eleven patients
reported grade 3 and 4 toxicity including hypernatremia in eight cases,
somnolence in two cases, and hypokalemia in one case. There were no chronic
toxicities, and the quality of life was very good. The largest group of
patients were represented by DIPG, GBM, and AA. The best results were obtained
in the DIPG and AA groups. In the DIPG group, CR was in 8.3%, PR was 25%,
median PFS was 4.8 months, median OS was 6.1 months, and OS at 6 months was
58.3%, at one year 25%, and 8.3% at two, five, and ten years. In the AA group,
PR was 12.5%, median PFS was 3.7 months, median OS was 4.7 months, and OS at 6
months was 37.5%, and 12.5%, at one, two, five, and ten years. In conclusion,
antineoplastons showed efficacy and acceptable toxicity in patients with
recurrent, refractory or progressive primary brain tumors.