A Case of Sustained Objective Response of Recurrent/Progressive Diffuse Intrinsic Pontine Glioma with Phenylbutyrate and Targeted Agents

Abstract

Diffuse intrinsic pontine glioma (DIPG) is the most common type of brainstem glioma and one of the most deadly brain tumors. DIPG in young adult patients is a rare disease for which treatment options are limited. Radiation therapy remains the standard-of-care for newly-diagnosed DIPG, but no established therapies for recurrent disease are available. This paper describes the results of treatment of a young adult patient diagnosed with DIPG that progressed after radiation therapy. Therapy included sodium phenylbutyrate (PB) in combination with the targeted agents: pazopanib, everolimus, erlotinib, and bevacizumab. The patient achieved a rapid partial response, which persisted over a year and five months. The patient opted to discontinue the therapy and thereafter elected chemotherapy, which resulted in a subsequent rapid progression and death within one month. The targeted treatment was associated with minor toxicity that included a Grade 2 skin rash and Grade 1 elevation of transaminases. In conclusion, a combination of PB and currently available targeted drugs may offer extended survival in patients with recurrent DIPG.

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Burzynski, S. , Burzynski, G. and Brookman, S. (2015) A Case of Sustained Objective Response of Recurrent/Progressive Diffuse Intrinsic Pontine Glioma with Phenylbutyrate and Targeted Agents. Journal of Cancer Therapy, 6, 40-44. doi: 10.4236/jct.2015.61006.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Ostrom, Q.T., Gittleman, H., Liao, P., Rouse, C., Chen, Y., et al. (2014) CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011. Neuro-Oncology, 16, iv1-iv63. http://dx.doi.org/10.1093/neuonc/nou223
[2] Donaldson, S.S., Laningham, F. and Fisher, P.G. (2006) Advances toward an Understanding of Brainstem Gliomas. Journal of Clinical Oncology, 24, 1266-1272. http://dx.doi.org/10.1200/JCO.2005.04.6599
[3] Hargrave, D., Bartels, U. and Bouffet, E. (2006) Diffuse Brainstem Glioma in Children: Critical Review of Clinical Trials. Lancet, 7, 241-248. http://dx.doi.org/10.1016/S1470-2045(06)70615-5
[4] Burzynski, S.R. (2007) Recent Clinical Trials in Diffuse Intrinsic Brainstem Glioma. Cancer Therapy, 5, 379-390.
[5] Guillamo, J.S., Monjour, A., Taillandier, L., Devaux, B., Varlet, P., et al. (2001) Brainstem Gliomas in Adults: Prognostic Factors and Classification. Brain, 124, 2528-2539.
http://dx.doi.org/10.1093/brain/124.12.2528
[6] Kesari, S., Kim, R.S., Markos, V., Drappatz, J., Wen, P.Y. and Pruitt, A.A. (2008) Prognostic Factors in Adult Brainstem Gliomas: A Multicenter, Retrospective Analysis of 101 Cases. Journal of Neuro-Oncology, 88, 175-183. http://dx.doi.org/10.1007/s11060-008-9545-1
[7] Barkovich, A.J., Krischer, J., Kun, L.E., Packer, R., Zimmerman, R.A., et al. (1990) Brain Stem Gliomas: A Classification System Based on Magnetic Resonance Imaging. Pediatric Neurosurgery, 16, 73-83.
http://dx.doi.org/10.1159/000120511
[8] Albright, A.L., Packer, R.J., Zimmerman, R., Rorke, L.B., Boyett, J. and Hammond, G.D. (2013) Magnetic Resonance Scans Should Replace Biopsies for the Diagnosis of Diffuse Brain Stem Gliomas: A Report from the Children’s Cancer Group. Neuro-Oncology, 15, 1026-1030.
[9] Brusilow, S.W., Danney, M., Waber, L.J., Batshaw, M., Burton, B., et al. (1984) Treatment of Episodic Hyperammonemia in Children with Inborn Errors of Urea Synthesis. New England Journal of Medicine, 310, 1630-1634. http://dx.doi.org/10.1056/NEJM198406213102503
[10] Iannitti, T. and Palmieri, B. (2011) Clinical and Experimental Applications of Sodium Phenylbutyrate. Drugs in R&D, 11, 227-249. http://dx.doi.org/10.2165/11591280-000000000-00000
[11] Burzynski, S.R. (1976) Antineoplastons: Biochemical Defense against Cancer. Physiological Chemistry and Physics, 8, 275-279.
[12] Burzynski, S.R. (1986) Antineoplastons: History of the Research (I). Drugs under Experimental and Clinical Research, 12, 1-9.
[13] Burzynski, S.R. (2004) The Present State of Antineoplaston Research (1). Integrative Cancer Therapies, 3, 47-58. http://dx.doi.org/10.1177/1534735403261964
[14] Burzynski, S.R. and Patil, S. (2014) The Effect of Antineoplastons A10 and AS2-1 and Metabolites of Sodium Phenylbutyrate on Gene Expression in Glioblastoma Multiforme. Journal of Cancer Therapy, 5, 929-945. http://dx.doi.org/10.4236/jct.2014.510099
[15] 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
[16] 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://dx.doi.org/10.1007/s00381-014-2401-z
[17] 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 and Review of Recent Trials. Journal of Cancer Therapy, 5, 565-577. http://dx.doi.org/10.4236/jct.2014.56065
[18] Burzynski, S.R., Janicki, T.J. and Burzynski, G.S. (2014) A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Recurrent Glioblastoma Multiforme. Final Report (Protocol BT-21). Journal of Cancer Therapy, 5, 946-956. http://dx.doi.org/10.4236/jct.2014.510100
[19] 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 Recurrent, Refractory or Progressive Primary Brain Tumors. Final Report (Protocol BT-22). Journal of Cancer Therapy, 5, 977-988. http://dx.doi.org/10.4236/jct.2014.510102
[20] Burzynski, S.R., Burzynski, G.S. and Janicki, T.J. (2014) Recurrent Glioblastoma Multiforme—A Strategy for Long-Term Survival. Journal of Cancer Therapy, 5, 957-976. http://dx.doi.org/10.4236/jct.2014.510101
[21] 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.
[22] Burzynski, S.R., Janicki, T.J., Burzynski, G.S. and Marszalek, A. (2013) Long-Term Survival (>13 years) in a Child with Recurrent Diffuse Pontine Gliosarcoma: A Case Report. Journal of Pediatric Hematology Oncology.
[23] Khuong-Quang, D.A., Buczkowicz, P., Rakopoulos, P., Liu, X.Y., Fontebasso, A.M., et al. (2012) K27M Mutation in Histone H3.3 Defines Clinically and Biologically Distinct Subgroups of Pediatric Diffuse Intrinsic Pontine Gliomas. Acta Neuropathologica, 124, 439-447. http://dx.doi.org/10.1007/s00401-012-0998-0

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