Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma Journal Article


Authors: Buckner, J. C.; Malkin, M. G.; Reed, E.; Cascino, T. L.; Reid, J. M.; Ames, M. M.; Tong, W. P. Y.; Lim, S.; Figg, W. D.
Article Title: Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma
Abstract: Objective: To assess the pharmacokinetics, toxicity, and efficacy of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261), Design: We initiated a phase II trial in order to determine whether evidence of antitumor activity of A10 and AS2-1 could be documented, Material and Methods: Patients with anaplastic astrocytoma or glioblastoma multiforme recurring after radiation therapy were eligible for enrollment in the trial, Patients received escalating doses of A10 and AS2-1 by multiple intermittent intravenous injections with use of a portable programmable pump to the target daily dose of 1.0 g/kg for A10 and of 0.4 g/kg for AS2-1, Results: Nine patients were treated, in six of whom the treatment response was assessable in accordance with protocol stipulations, No patient demonstrated tumor regression. Reversible grade 2 or 3 neurocortical toxicity, consisting of transient somnolence, confusion, and exacerbation of an underlying seizure disorder, was noted in five patients, Mean steady-state plasma concentrations of phenylacetate and phenylacetylglutamine after escalation to the target doses of A10 and AS2-1 were 177 +/- 101 mu g/mL and 302 +/- 102 mu g/mL, respectively, Patients who exhibited confusion tended to have higher phenylacetate levels, Conclusion: Although we could not confirm any tumor regression in patients in this study, the small sample size precludes definitive conclusions about treatment efficacy. Antineoplaston-related toxicity was acceptable in most patients with appropriate dose modification, although severe neurocortical toxicity may occur. Steady-state plasma concentrations of phenylacetate with use of A10 and AS2-1 were similar to those reported with use of similar doses of phenylacetate alone.
Keywords: differentiation; cells; growth; derivatives; inhibition; alpha; phenylacetate; phenylketonuria; cancer
Journal Title: Mayo Clinic Proceedings
Volume: 74
Issue: 2
ISSN: 0025-6196
Publisher: Mayo Clinic Proceedings  
Date Published: 1999-01-01
Start Page: 137
End Page: 145
Language: English
ACCESSION: WOS:000078606200005
PROVIDER: wos
PUBMED: 10069350
DOI: 10.4065/74.2.137
Notes: Article -- Source: Wos
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MSK Authors
  1. William Ping-Yiu Tong
    130 Tong
  2. Mark Malkin
    26 Malkin