跳至主要内容

Preliminary Findings on the Use of Targeted Therapy with Pazopanib and Other Agents in Combination with Sodium Phenylbutyrate in the Treatment of Glioblastoma Multiforme

Read full paper at:
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=52600#.VJyu-cCAM4

The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (RGBM) are much worse, with the majority dying within 6 months. This publication provides a brief description of the treatment of 11 GBM patients treated with sodium phenylbutyrate (PB) in combination with pazopanib, m-TOR inhibitors, and other agents. The treatment was associated with tolerable side effects and resulted in objective responses in 54.5% of cases (complete response 18.2%, partial response 36.3%) and 27.3% cases of stable disease. The preferable treatment regimen consisted of PB, pazopanib, dasatinib, everolimus, and bevacizumab (BVZ). For various reasons not all patients were compliant with the treatment regimen. In patients who strictly complied with the treatment plan, all responded as CR or PR. Based on preliminary findings, the authors propose further phase I/II clinical trials with PB in combination with pazopanib, dasatinib, everolimus, and BVZ in patients with RGBM who failed standard surgery, radiation therapy and chemotherapy. With proper dose reductions, the treatment appears to be well-tolerated. Molecular profiling of patient subgroups with favorable genomic signatures may help to select patients for future studies.
Cite this paper
Burzynski, S. , Janicki, T. , Burzynski, G. and Brookman, S. (2014) Preliminary Findings on the Use of Targeted Therapy with Pazopanib and Other Agents in Combination with Sodium Phenylbutyrate in the Treatment of Glioblastoma Multiforme. Journal of Cancer Therapy, 5, 1423-1437. doi: 10.4236/jct.2014.514144. 
 

[1] Ostrom, Q.T., Gittleman, H., Farah, P., Ondracek, A., Chen, Y., Wolinsky, Y., et al. (2013) CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States 2006-2010. Neuro-Oncology, 15, ii1-ii56. http://dx.doi.org/10.1093/neuonc/not151
[2] Ohka, F., Natsume, A. and Wakabayashi, T. (2012) Current Trends in Targeted Therapies for Glioblastoma Multiforme. Neurology Research International, 2012, Article ID: 878425.
http://dx.doi.org/10.1155/2012/878425
[3] Olson, J.J., Nayak, L., Ormond, D.R., Wen, P.Y., Kalkanis, S.N. and Ryken, T.C. (2014) The Role of Targeted Therapies in the Management of Progressive Glioblastoma. Journal of Neuro-Oncology, 118, 557-599. http://dx.doi.org/10.1007/s11060-013-1339-4
[4] Stupp, R., Mason, W.P., van den Bent, M.J., Weller, M., Fisher, B., Taphoorn, M.J.B., et al. (2005) Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New England Journal of Medicine, 352, 987-996. http://dx.doi.org/10.1056/NEJMoa043330
[5] Stupp, R., Hegi, M.E., Mason, W.P., van den Bent, M.J., Taphoorn, M.J., Janzer, R.C., et al. (2009) Effects of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy Alone on Survival in Glioblastoma in a Randomized Phase III Study: 5-Year Analysis of the EORTC-NCIC Trial. Lancet Oncology, 10, 459-466. http://dx.doi.org/10.1016/S1470-2045(09)70025-7
[6] Burzynski, S.R. (1976) Antineoplastons: Biochemical Defense against Cancer. Physiological Chemistry and Physics, 8, 275-279.
[7] Burzynski, S.R. (1986) Antineoplastons—History of the Research (I). Drugs under Experimental Clinical Research, 12, 1-9.
[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 Glioma Based on Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Brainstem Glioma. Childs Nervous System, 30, 2051-2061.
http://dx.doi.org/10.1007/s00381-014-2401-z
[11] 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. http://dx.doi.org/10.4236/jct.2014.56065
[12] 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
[13] Burzynski, S.R., Janicki, T.J., Burzynski, G.S., 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.
http://dx.doi.org/10.4236/jct.2014.510102
[14] 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
[15] Brusilow, S.W., Danney, M., Waber, L.J., Batshaw, M., Burton, B., Levitsky, L., 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
[16] 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
[17] 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
[18] Sturm, D., Witt, H., Hovestadt, V., Khuong-Quang, D.A., Jones, D.T., Konermann, C., et al. (2012) Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma. Cancer Cell, 22, 425-437. http://dx.doi.org/10.1016/j.ccr.2012.08.024
[19] Phuphanich, S., Baker, S.D., Grossman, S.A., Carson, K.A., Gilbert, M.R., Fisher, J.D., et al. (2005) Oral Sodium Phenylbutyrate in Patients with Recurrent Malignant Gliomas: A Dose Escalation and Pharmacologic Study. Neuro-Oncology, 7, 177-182. http://dx.doi.org/10.1215/S1152851704000183
[20] 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.
[21] 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
[22] Prados, M.D. (2014) “We Will Know if When We See It”; Bevacizumab and Glioblastoma. Neuro-Oncology, 16, 469-470. http://dx.doi.org/10.1093/neuonc/nou036
[23] Gerber, N.K., Goenka, A., Turcan, S., Reyngold, M., Makarov, V., Kannan, K., et al. (2014) Transcriptional Diversity of Long-Term Glioblastoma Survivors. Neuro-Oncology, 16, 1186-1195.
http://dx.doi.org/10.1093/neuonc/nou043                     eww141225lx
标签：

评论

发表评论

此博客中的热门博文

A Comparison of Methods Used to Determine the Oleic/Linoleic Acid Ratio in Cultivated Peanut (Arachis hypogaea L.)

Cultivated peanut ( Arachis hypogaea L.) is an important oil and food crop. It is also a cheap source of protein, a good source of essential vitamins and minerals, and a component of many food products. The fatty acid composition of peanuts has become increasingly important with the realization that oleic acid content significantly affects the development of rancidity. And oil content of peanuts significantly affects flavor and shelf-life. Early generation screening of breeding lines for high oleic acid content greatly increases the efficiency of developing new peanut varieties. The objective of this study was to compare the accuracy of methods used to classify individual peanut seed as high oleic or not high oleic. Three hundred and seventy-four (374) seeds, spanning twenty-three (23) genotypes varying in oil composition (i.e. high oleic (H) or normal/not high oleic (NH) inclusive of all four peanut market-types (runner, Spanish, Valencia and Virginia), were individually tested ...
发表评论
阅读全文

Location Optimization of a Coal Power Plant to Balance Costs against Plant’s Emission Exposure

Fuel and its delivery cost comprise the biggest expense in coal power plant operations. Delivery of electricity from generation to consumers requires investment in power lines and transmission grids. Placing a coal power plant or multiple power plants near dense population centers can lower transmission costs. If a coalmine is nearby, transportation costs can also be reduced. However, emissions from coal plants play a key role in worsening health crises in many countries. And coal upon combustion produces CO 2 , SO 2 , NO x , CO, Metallic and Particle Matter (PM10 & PM2.5). The presence of these chemical compounds in the atmosphere in close vicinity to humans, livestock, and agriculture carries detrimental health consequences. The goal of the research was to develop a methodology to minimize the public’s exposure to harmful emissions from coal power plants while maintaining minimal operational costs related to electric distribution losses and coal logistics. The objective was...
发表评论
阅读全文

Evaluation of the Safety and Efficacy of Continuous Use of a Home-Use High-Frequency Facial Treatment Appliance

At present, many home-use beauty devices are available in the market. In particular, many products developed for facial treatment use light, e.g., a flash lamp or a light-emitting diode (LED). In this study, the safety of 4 weeks’ continuous use of NEWA TM , a high-frequency facial treatment appliance, every alternate day at home was verified, and its efficacy was evaluated in Japanese individuals with healthy skin aged 30 years or older who complained of sagging of the facial skin.  Transepidermal water loss (TEWL), melanin levels, erythema levels, sebum secretion levels, skin color changes and wrinkle improvement in the facial skin were measured before the appliance began to be used (study baseline), at 2 and 4 weeks after it had begun to be used, and at 2 weeks after completion of the 4-week treatment period (6 weeks from the study baseline). In addition, data obtained by subjective evaluation by the subjects themselves on a visual analog scale (VAS) were also analyzed. Fur...
发表评论
阅读全文