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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

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DOI: 10.4236/jct.2014.56065    3,378 Downloads   4,620 Views   Citations

ABSTRACT

Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.

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Burzynski, S. , Janicki, T. , Burzynski, G. 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. doi: 10.4236/jct.2014.56065.

References

[1] 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. Cancer Journal for Clinicians, 60, 166-193. http://dx.doi.org/10.3322/caac.20069
[2] 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
[3] 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.
http://dx.doi.org/10.1093/neuonc/nor039
[4] 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 FuturisticPerspective. Journal of Neuro-Oncology, 75, 253-266. http://dx.doi.org/10.1007/s11060-005-6747-7
[5] CBTRUS (2013) CBTRUS Statistical Report Supplement 2013: Primary Brain and Central Nervous System Tumors Diagnosed in the United States 2006-2010. Neuro-Oncology, 15, ii1-ii56.
[6] Burzynski, S.R. (2004) The Present State of Antineoplaston Research (1). Integrative Cancer Therapies, 3, 47-58. http://dx.doi.org/10.1177/1534735403261964
[7] Burzynski, S.R., Kubove, E. and Burzynski, B. (1992) Phase II Clinical Trials of antineoplastons A10 and AS2-1 Infusions in Astrocytoma. In: Adam, D., Ed., Recent Advances in Chemotherapy, Futuramed Publishers, Munich, 2506-2507.
[8] Hawkins, M.G. and Friedman, M.A. (1992) National Cancer Institute's Evaluation of Unconventional Cancer Treatments. Journal of the National Cancer Institute, 84, 1699.
http://dx.doi.org/10.1093/jnci/84.22.1699
[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 Glioma Based on Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Brainstem Glioma. Child’s Nervous System.
http://link.springer.com/article/10.1007/s00381-014-2401-z
[11] Burzynski, S.R., Janicki, T.J., Burzynski, G.S. and Marszalek, A. (2013) Long-Term Survival (>13 Years) in a Child with Recurrent Diffuse Intrinsic Pontine Glioma: A Case Report. Journal of Pediatric Hematology/Oncology. http://journals.lww.com/jpho-online/Abstract/publishahead/Long_term_Sur- vival___13_Years__in_a_Child_With.98997.aspx http://dx.doi.org/10.1097/MPH.0000000000000 020
[12] Chang, S.M., Kuhn, J.G., Robins, H.I., Schold, S.C., Spence, A.M., Berger, M.S., Mehta, M.P., Bozik, M.E., Pollack, I., Schiff, D., Gilbert, M., Rankin, C. and Prados, M.D. (1999) Phase II Study of Phenylacetate in Patients with Recurrent Malignant Flioma: A North American Brain Tumor Consortium Report. Journal of Clinical Oncology, 17, 984-990.
[13] Wen, P.Y., Macdonald, D.R., Reardon, D.A., Cloughesy, T.F., Sorensen, A.G., 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.
http://dx.doi.org/10.1200/JCO.2009.26.3541
[14] Weller, M., Cloughesy, T., Perry, J.R. and Wick, W. (2013) Standards of Care for Treatment of Recurrent Glioblastoma—Are We There Yet? Neuro-Oncology, 15, 4-27.
http://dx.doi.org/10.1093/neuonc/nos273
[15] Lashford, L.S., Thiesse, P., Jouvet, A., Jaspan, T., Couanet, D., Griffiths, P.D., Doz, F., Ironside, J., Robson, K., Hobson, R., Dugan, M., Pearson, A.D.J., Vassal, G. and Frappaz, D. (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
[16] Dreyer, Z.E., Kadota, R.P., Stewart, C.F., Friedman, H.S., Mahoney, D.H., et al. (2003) Phase 2 Study of Idarubicin in Pediatric Brain Tumors: Pediatric Oncology Group Study POG 9237. Neuro-Oncology, 5, 261-267. http://dx.doi.org/10.1215/S115285170200056X
[17] Warren, K., Jakacki, R., Widemann, B., Aikin, A., Libucha, M., et al. (2006) Phase II Trial of Intravenous Lobradimil and Carboplatin in Childhood Brain Tumors: A Report from the Children’s Oncology Group. Cancer Chemotherapy and Pharmacology, 58, 343-347.
http://dx.doi.org/10.1007/s00280-005-0172-7
[18] Fouladi, M., Nicholson, H.S., Zhou, T., Laningham, F., Helton, K.J., et al. (2007) A Phase II Study of the Farnesyl Transferase Inhibitor, Tipifarnib, in Children with Recurrent or Progressive High-Grade Glioma, Medulloblastoma/ Primitive Neuroectodermal Tumor, or Brainstem Glioma: A Children's Oncology Group Study. Cancer, 110, 2535-2541. http://dx.doi.org/10.1002/cncr.23078
[19] Gururangan, S., Chi, S.N., Poussaint, T.Y., Onar-Thomas, A., Gilbertson, R.J., et al. (2010) Lack of Efficacy of Bevacizumab Plus Irinotecan in Children with Recurrent Malignant Glioma and Diffuse Brainstem Glioma: A Pediatric Brain Tumor Consortium Study. Journal of Clinical Oncology, 28, 3069-3075. http://dx.doi.org/10.1200/JCO.2009.26.8789
[20] Nicholson, H.S., Kretschmar, C.S., Krailo, M., Bernstein, M., Kadota, R., 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. http://dx.doi.org/10.1002/cncr.22961
[21] Warren, K.E., Gururangan, S., Geyer, J.R., McLendon, R.E., Poussaint, T.Y., 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

  
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