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

Abstract

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.

Destabilization of Abnormal Methylation Enzymes: Nature’s Way to Eradicate Cancer Stem Cells

“…Nevertheless, it has demonstrated therapeutic efficacy on often untreatable brain tumors [44,45]. It's benefits were enhanced when used in combination with STIs [46,47], which were effective in µM concentrations [16].…”

Estimation for finite mixture of simplex models: applications to biomedical data

“…In the next section, an individual image taken from Burzynski et al (2014) in the treatment of an inoperable, recurrent, persistent or progressed GBM is explored in detail.…”

“…An MRI was undertaken by patient number 4 of Burzynski et al (2014) before the treatment of 'pazopanib and other agents, in combination with administered sodium phenylbutyrate', and is shown in Figure 5a. There were estimated five zero-inflated models mixturing beta and simplex distributions, respectively (Table 4).…”

A Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Brainstem Gliomas. The Report on Non-Diffuse Intrinsic Pontine Glioma (Protocol BT-11)

“…Serious complications in using ANP in RPDIPG included Grade 3 hypernatremia in 18%, somnolence in 12% and hypokalemia, urinary incontinence and fatigue in 6% [13]. The medications from the ANP group do not cause any problems of interactions with other conventional therapies [18] [19].…”