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

Jan Craig Buckner, Mark G. Malkin, Eddie Reed, Terrence L. Cascino, Joel M Reid, Matthew M. Ames, William P Y Tong, Silam Lim, William D. Figg

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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 μg/mL and 302 ± 102 μg/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.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalMayo Clinic Proceedings
Volume74
Issue number2
StatePublished - 1999

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  • Medicine(all)

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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. (1999). Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma. Mayo Clinic Proceedings, 74(2), 137-145.