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

Stanislaw R Burzynski,Gregory S Burzynski,Tomasz J Janicki

doi:10.4236/jct.2015.612116

Abstract

Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, BT-06, which was transferred from the National Institutes of Health (NIH). Protocol BT-09 was designed for different types of primary brain tumors in adults that were not curable by standard treatment. The study was designed as a single arm, two-stage, phase II trial of ANP as a monotherapy in a high-risk, poor-prognosis population. The total number of registered subjects was 40. The majority of patients were diagnosed with high-grade tumors (N = 33). In this group, 12 patients carried diagnosis of anaplastic astrocytoma (AA) and 11 patients of glioblastoma. In the group of low-grade tumors (N = 7), there were 6 cases of low-grade glioma, and 1 neurocytoma grade 2. A group of 12 patients did not receive any prior treatment, 12 patients had surgical resection only, 5 patients received radiation therapy (RT) only, and 11 patients received both RT and chemotherapy. The median duration of ANP was 16.6 weeks. The median dosage of A10 was 7.16 g/kg/d and AS2-1 was 0.27 g/kg/d. Responses were accessed by gadolinium-enhanced magnetic resonance imaging (MRI). Objective responses (OR) in all patients were 22.5% and in the AA group were 41.7% of patients. The median progression-free survival (PFS) in the AA group was 5.4 months. The median overall survival (OS) was 12.7 months and OS at 1 and 2 years was 54.5% and 45.5% correspondingly. The treatment was well-tolerated with reversible grade 3 and 4 toxicities in 35% of all patients (N = 40). In conclusion, the study reached efficacy endpoint and ANP was well-tolerated and compared favorably to the current treatment of AA.

Highlights

Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine and phenylacetic acid [1]
In 1993, a Phase II clinical trials program began according to protocols based on initial Protocol BT-06 which was transferred from the National Institutes of Health (NIH) to Burzynski Research Institute, Inc. (BRI) [3]
GBM was represented by 11 patients and the additional high-grade tumors included primitive neuroectodermal tumors (PNET) N = 3, diffuse intrinsic pontine glioma (DIPG) N = 3, and tectal glioma (TG) N = 1

Summary

Introduction

Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine and phenylacetic acid [1]. Phase II studies of ANP injections in astrocytoma began in 1988 and documented objective responses (OR) in 30% of 20 patients diagnosed with anaplastic astrocytoma (AA), low-grade astrocytoma (LGA), and diffuse intrinsic pontine glioma (DIPG) [2]. BT-09 and BT-10 were designed for different types of primary brain tumors which were not curable by standard treatment in adults (BT-09) and children (BT-10). Numerous additional protocols dealt with the treatment of specific types of brain tumors in children and adults and colorectal cancer [4]-[18]. The aim of this single arm study is to assess the efficacy and safety of ANP in adults who have different types of incurable primary brain tumors. Special emphasis was directed to high-grade tumors (82.5% of patients) with attention to the subgroup of AA

Objectives

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Conclusion