A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Recurrent Glioblastoma Multiforme: Final Report (Protocol BT-21)

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 * Corresponding author. S. R. Burzynski et al. 94717.5% 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.

A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Primary Brain Tumors—Final Report (Protocol BT-09)

“…The additional inclusion, exclusion and removal from the study criteria were the same as in the other brain tumor study [11]. All study subjects and/or guardians read, understood, and signed written informed consent prior to enrollment.…”

“…The patients were advised to continue the treatment until the maximum response was achieved and for eight months thereafter. The details of administration of ANP were published before [11].…”

“…The baseline provided the reference for determining response outcomes to the treatment. The details of laboratory tests and additional examinations were published before [11]. Toxicity was evaluated in all patients enrolled in the study (intent-to-treat (ITT) population).…”

Long-Term Survival Over 21 Years and Pathologically Confirmed Complete Response in Pediatric Anaplastic Astrocytoma: A Case Report

“…ANP A10 capsules contain 500 mg of 3-phenylacetylamino-2,6-piperidinedione, which is metabolized in the body to 4:1 ratio of PG, and isoPG and AS2-1 capsules contain 500 mg of 4:1 ratio of PN and PG [6]. Interim results of the phase II studies have already been reported as well as case reports of long-term survival of HGG and diffuse intrinsic pontine glioma (DIPG) [3,[7][8][9][10][11][12][13][14][15][16]. Here, we discuss a case of very long survival (over 21 years) of PAA with pathologically-confirmed complete response (CR).…”

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

“…A recently published phase II study evaluated the safety and efficacy of ANP A10 and AS2-1 in recurrent high-grade glioma, with special emphasis to RGBM. Objective responses (OR) were determined in 17% of eligible patients, overall survival (OS) was 65.5% at 6 months; 56.7% at 9 months, 39% at 1 year and 4.4% at 2, 5, and 10 years [12].…”