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.
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Article Info
Footnotes
This study was supported in part by grants U01 CA 69912, MOl RR 00585, P30 CA 15083, and CM 07311-04 from the National Institutes of Health, Public Health Service, and by the Linse Bock Foundation.
Identification
Copyright
© 1999 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
