Abstract
Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special attention to RGBM patients treated with Antineoplastons (ANP) A10 and AS2-1 injections. The study was conducted according to Protocol BT-21, which accrued patients who failed standard radiation therapy (RT) and chemotherapy. There were 40 candidates registered in the study. Among the intent-to-treat (ITT) population, there were 30 cases of RGBM that progressed during and after prior treatment, 4 patients with anaplastic astrocytoma (AA), 1 with anaplastic mixed glioma (AMG), and 5 with persistent GBM. The aim of this paper is to evaluate the responses, survival and toxicity of all 40 patients, the efficacy in 30 patients with RGBM, and in 24 patients with RGBM who received at least 28 days of ANP (ERGBM). All RGBM patients were treated before with RT and chemotherapy, except one patient who only had surgery (patient refused radiation). In this group, 63% had one recurrence, 30% had two recurrences, and 7% had three recurrences. The median duration of ANP and ITT was 12 weeks and the median dosage of ANP A10 was 6.52 g/kg/d and ANP AS2-1 was 0.23 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging (MRI) repeated every eight weeks. In the ITT population, objective responses (ORs) were determined in 10% of cases (complete response—CR, and partial response—PR in 5% each). Progression-free survival (PFS) in ITT at six months was 17.5%. Overall survival (OS) was 28.3% at one year, 2.6% at two years, five and ten years. In the RGBM population, objective responses (ORs) were determined in 13.3% of cases (CR and PR in 6.7% each). PFS in RGBM at six months was 16.7%. OS was 34.7% at one year, 3.47% at two years, five and ten years. In the ERGBM population, ORs were determined in 16.7% of cases (CR and PR in 8.3% each). PFS in ERGBM at six months was 20.8%, OS was 39.3% at one year, 4.4% at two years, five and ten years. The treatment was well-tolerated with reversible Grades 3 and 4 toxicity in 17.5% of patients (7 patients who experienced multiple toxicities) and no chronic toxicity. In conclusion, the study reached efficacy endpoint. ANP is well-tolerated and compares favorably to the current treatment for RGBM.
Highlights
Glioblastoma multiforme (GBM) is the most common highly-malignant brain tumor with an average annual incidence in the U.S of over 50,000 cases [1]
Patients were removed from the study if 1) progressive disease (PD) developed, 2) if toxicity levels became unacceptable, 3) if the subject developed a concurrent illness that interfered with therapy, 4) if the subject or guardian asked to be removed from the study or became non-compliant with the study criteria, and 5) if the subject completed at least 8 months of treatment after determination of complete response (CR), partial response (PR) or stable disease (SD)
Forty candidates were registered in the study (ITT population)
Summary
Glioblastoma multiforme (GBM) is the most common highly-malignant brain tumor with an average annual incidence in the U.S of over 50,000 cases [1]. It is currently thought that GBM develops through the progressive accumulation of epigenetic and genetic changes that help the cells to escape destruction by molecular mechanisms of the body [2]. There is vast literature indicating that environmental exposure is associated with increased incidence of GBM. Ionizing radiation is the only environmental factor that is consistently associated with the development of GBM [2] [4]. The interesting results were found in epidemiologic studies of association between allergies and cancer [9]. GBM has inherent feature to progress due to accumulation of epigenetic and genetic abnormalities over time, which is similar to other aggressive types of cancer [11]. Unstable GBM genome undergoes continuous changes and converts to RGBM after standard-of-care treatment [13] [14]
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