Mayo Clinic proceedings · 1999
Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma.
Клиническое исследованиеКлиническое исследование II фазыСтатьяПоддержка исследования: вне правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
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Buckner J C, Malkin M G, Reed E, Cascino T L, Reid J M, Ames M M, Tong W P, Lim S, Figg W D
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAntineoplastic AgentsAstrocytomaBenzeneacetamidesBrain NeoplasmsConfusionDisorders of Excessive SomnolenceDrug Administration ScheduleDrug CombinationsFemaleGlioblastomaGlutamineHumansInjections, IntravenousMaleMiddle AgedPatient SelectionPhenylacetatesPiperidonesSeizuresSeverity of Illness IndexTreatment Outcome