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

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.