TITLE:
A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Recurrent Glioblastoma Multiforme: Final Report (Protocol BT-21)
AUTHORS:
Stanislaw R. Burzynski, Tomasz J. Janicki, Gregory S. Burzynski
KEYWORDS:
Antineoplastons A10 and AS2-1, Recurrent Glioblastoma Multiforme, Phase II Clinical Trial, Survival in Glioblastoma
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.10,
September
10,
2014
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, fiveand ten years. In the ERGBM
population, ORs were determined in 16.7% of cases (CR and PR in8.3% 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.