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)


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.

Share and Cite:

Burzynski, S. , Janicki, T. , Burzynski, G. , Marszalek, A. and Brookman, S. (2014) 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). Journal of Cancer Therapy, 5, 977-988. doi: 10.4236/jct.2014.510102.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Porter, K.R., McCarthy, B.J., Freels, S., et al. (2010) Prevalence Estimates for Primary Brain Tumors in the United States by Age, Gender, Behavior and Histology. Neuro-Oncology, 12, 520-527.
[2] CBTRUS (2013) CBTRUS Statistical Report Supplement 2013: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2006-2010. Neuro-Oncology, 15, ii1-ii56.
[3] Broniscer, A. and Gajjar, A. (2004) Supratentorial High-Grade Astrocytoma and Diffuse Brainstem Glioma: Two Challenges for the Pediatric Oncologist. Oncologist, 9, 197-206.
[4] Stupp, R., Mason, W.P., van den Bent, M.J., Weller, M., Fisher, B., et al. (2005) Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. The New England Journal of Medicine, 352, 987-996. http://dx.doi.org/10.1056/NEJMoa043330
[5] Wick, W., Weller, M., Weiler, M., Batchelor, T., Yung, A.W. and Platten, M. (2011) Pathway Inhibition: Emerging Molecular Targets for Treating Glioblastoma. Neuro-Oncology, 13, 566-579.
[6] Hargrave, D., Bartels, U. and Bouffet, E. (2006) Diffuse Brainstem Glioma in Children: Critical Review of Clinical Trials. Lancet, 7, 241-248.
[7] Finlay, J.L. and Zacharoulis, S. (2005) The Treatment of High Grade Gliomas and Diffuse Intrinsic Pontine Tumors of Childhood and Adolescence: A Historical and Futuristic Perspective. Journal of Neuro-Oncology, 75, 253-266. http://dx.doi.org/10.1007/s11060-005-6747-7
[8] Burzynski, S.R. (2004) The Present State of Antineoplaston Research (1). Integrative Cancer Therapies, 3, 47-58. http://dx.doi.org/10.1177/1534735403261964
[9] Burzynski, S.R. (2006) Treatments for Astrocytic Tumors in Children: Current and Emerging Strategies. Pediatric Drugs, 8, 167-168. http://dx.doi.org/10.2165/00148581-200608030-00003
[10] Burzynski, S.R., Janicki, T.J., Burzynski, G.S. and Marszalek, A. (2014) The Response and Survival of Children with Recurrent Diffuse Intrinsic Pontine Gliomas Based on Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Brainstem Glioma. Child’s Nervous System, Published Online.
[11] Burzynski, S.R., Janicki, T.J., Burzynski, G.S. and Marszalek, A. (2014) Long-Term Survival (>13 Years) in a Child with Recurrent Diffuse Intrinsic Pontine Glioma: A Case Report. Journal of Pediatric Hematology/Oncology, Published Oniline.
[12] Burzynski, S.R., Janicki, T.J., Burzynski, G.S. and Marszalek, A. (2014) A Phase II Study of Antineoplastons A10 and AS2-1 in Children with High-Grade Glioma. Final Report (Protocol BT-06), and Review of Recent Trials. Journal of Cancer Therapy, 5, 565-577.
[13] Packer, R.J., Boyett, J.M., Zimmerman, R.A., Rorke, L.B., Kaplan, A.M., Albright, A.L., et al. (1993) Hyperfractionated Radiation Therapy (72 Gy) for Children with Brain Stem Gliomas. A Childrens Cancer Group Phase I/II Trial. Cancer, 72, 1414-1421.
[14] Albright, A.L., Packer, R.J., Zimmerman, R., Rorke, L.B., Boyett, J. and Hammond, G.D. (1993) Magnetic Resonance Scans Should Replace Biopsies for the Diagnosis of Diffuse Brain Stem Gliomas: A Report from the Children’s Cancer Group. Neurosurgery, 33, 1026-1030.
[15] Wen, P.Y., Macdonald, D.R., Reardon, D.A., Cloughesy, T.F., Sorensen, A.G., Galanis, E., et al. (2010) Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group. Journal of Clinical Oncology, 28, 1963-1972.
[16] Choux, M., Lena, G. and Do, L. (2000) Brainstem Tumors. In: Choux, M., Di Rocco, C. and Hockley, A., Eds., Pediatric Neurosurgery, Churchill Livingstone, New York, 471-491.
[17] Leach, P.A., Estlin, E.J., Coope, D.J., Thorne, J.A. and Kamaly-Asl, I.D. (2008) Diffuse Brainstem Gliomas in Children: Should We or Shouldn’t We Biopsy? British Journal of Neurosurgery, 22, 619-625. http://dx.doi.org/10.1080/02688690802366198
[18] Chang, S.M., Kuhn, J.G., Robins, H.I., Schold, S.C., Spence, A.M., Berger, M.S., et al. (1999) Phase II Study of Phenylacetate in Patients with Recurrent Malignant Glioma: A North American Brain Tumor Consortium Report. Journal of Clinical Oncology, 17, 984-990.
[19] Weller, M., Cloughesy, T., Perry, J.R. and Wisk, W. (2013) Standards of Care for Treatment of Recurrent Glioblastoma—Are We There Yet? Neuro-Oncology, 15, 4-27.
[20] Van Meir, E.G., Hadjipanayis, C.G., Norden, A.D., Shu, H.K., Wen, P.Y. and Olson, J.J. (2010) Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma. CA: A Cancer Journal for Clinicians, 60, 166-193. http://dx.doi.org/10.3322/caac.20069
[21] Lashford, L.S., Thiesse, P., Jouvet, A., Jaspan, T., Couanet, D., Griffiths, P.D., et al. (2002) Temozolomide in Malignant Gliomas of Childhood: A United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. Journal of Clinical Oncology, 20, 4684-4691. http://dx.doi.org/10.1200/JCO.2002.08.141
[22] Nicholson, H.S., Kretschmar, C.S., Krailo, M., Bernstein, M., Kadota, R., Fort, D., et al. (2007) Phase 2 Study of Temozolomide in Children and Adolescents with Recurrent Central Nervous System Tumors. A Report from the Children’s Oncology Group. Cancer, 110, 1542-1550.
[23] Warren, K.E., Gururangan, S., Geyer, J.R., McLendon, R.E., Poussaint, T.Y., Wallace, D., et al. (2012) A Phase II Study of 06-Benzylguanine and Temozolomide in Pediatric Patients with Recurrent or Progressive High-Grade Gliomas and Brainstem Gliomas: A Pediatric Brain Tumor Consortium Study. Journal of Neuro-Oncology, 106, 643-649. http://dx.doi.org/10.1007/s11060-011-0709-z

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.