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Phase
II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients
with recurrent glioma
Buckner JC, Malkin MG, Reed E, Cascino TL, Reid JM, Ames MM, Tong WP,
Lim S, Figg WD
Department of Oncology, Mayo Clinic Rochester, Minnesota
55905, USA
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 microg/mL and 302+/-102 microg/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.
PMID:
10069350 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10069350
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