Mayo Clinic Proceedings Home

Phase II Study of Antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in Patients With Recurrent Glioma


      To assess the pharmacokinetics, toxicity, and efficacy of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261).


      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.


      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.


      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.
      CT (computed tomographic), HPLC (high-performance liquid chromatographic), MRI (magnetic resonance imaging), PA (phenylacetate), PAG (phenylacetylglutamine)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Green S
        ‘Antineoplastons’: an unproved cancer therapy.
        JAMA. 1992; 267: 2924-2928
        • Burzynski SR
        • Kubove E
        • Burzynski B
        Phase II clinical trials of antnieoplaston A10 and AS2-1 infusions in astrocytoma.
        in: Adam D Buchner T Rubinstein E Recent Advances m Chemotherapy. Futuramed Publishers, Munich1991: 2506-2507
      1. Antineoplastons: request for phase II trials in CNS malignancies.
        CTEPLett. 1992 May; 10: 10
        • Samid D
        • Shack S
        • Sherman LT
        Phenylacetate: a novel nontoxic inducer of tumor cell differentiation.
        Cancer Res. 1992; 52: 1988-1992
        • Samid D
        • Ram Z
        • Hudglns WR
        • Shack S
        • Liu L
        • Walbrldge S
        • et al.
        Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria.
        Cancer Res. 1994; 54: 891-895
        • Stockhammer G
        • Manley GT
        • Johnson R
        • Rosenblum MK
        • Samid D
        • Ueberman FS
        Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate.
        J Neurosurg. 1995; 83: 672-681
        • Samid D
        • Yeh T-J
        • Shack S
        Interferon in combination with antitumourigenic phenyl derivatives: poterrtiation of IFNα activity in-vrtro.
        Br J Haematol. 1991; 79: 81-83
        • Ram Z
        • Samid D
        • Walbrldge S
        • Oshlro EM
        • Viola JJ
        • Tao-Cheng JH
        • et al.
        Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate.
        Cancer Res. 1994; 54: 2923-2927
        • Danesi R
        • Nardini D
        • Basolo F
        • Del Tacca M
        • Samid D
        • Myers CE
        Phenylacetate inhibits protein isoprenylation and growth of the androgen-independent LNCaP prostate cancer cells transfected with the T24 Ha-ras oncogene.
        Mol Pharmacol. 1996; 49: 972-979
        • Hudglns WR
        • Shack S
        • Myers CE
        • Samid D
        Cytostatc activity of phenylacetate and derivatives against tumor cells: correlation with lipophilicity and inhibition of protein prenylation.
        Blochem Pharmacol. 1995; 50: 1273-1279
        • Liu L
        • Hudglns WR
        • Miller AC
        • Chen LC
        • Samid D
        Transcriptional upregulation of TGF-alpha by phenylacetate and phenylbutyrate is associated with differentiation of human melanoma cells.
        Cytokine. 1995; 7: 449-456
        • Kleihues P
        • Burger PC
        • Schelthauer BW
        Histological Typing of Tumours of the Central Nervous System. 2nd ed. Springer-Verlag, Berlin1993
        • Fleming TR
        One-sample multiple testing procedure for phase II clinical trials.
        Biometrics. 1982; 38: 143-151
        • Brusilow SW
        Phenylacetylglutamine may replace urea as a vehicle for waste nitrogen excretion.
        PediatrRes. 1991; 29: 147-150
        • Thibault A
        • Flgg WD
        • McCall N
        • Samid D
        • Myers CE
        • Cooper MR
        A simultaneous assay of the differentiating agents, phenylacetic acid and phenylbutyric acid, and one of their metabolites, phenylacetylglutamine, by reversed-phase, high performance liquid chromatogra-phy.
        J Liquid Chromatogr. 1994; 17: 2895-2900
        • Sherwln CP
        • Kennard KS
        Toxicity of phenylacetic acid.
        J Biol Chem. 1919; 40: 259-264
        • Loo YH
        • Potempska A
        • Wlsniewski HM
        A biochemical explanation of phenyl acetate neurotoxicity in experimental phenylketonuria.
        J Neurochem. 1985; 45: 1596-1600
        • Potempska A
        • Loo YH
        • Wlsnlewski HM
        On the possible mechanism of phenylacetate neurotoxicity: inhibition of choline acetyltransferase by phenytacetyl-CoA.
        J Neurochem. 1984; 42: 1499-1501
        • Thibault A
        • Cooper MR
        • Figg WD
        • Verizon DJ
        • Sartor AO
        • Tompkins AC
        • et al.
        A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer.
        Cancer Res. 1994; 54: 1690-1694
        • Burzynski SR
        Antineoplastons; history of the research (1).
        Drugs Exp Clin Res. 1986; 12: l-9
        • Soltysiak-Pawluezuk D
        • Buriynskl SR
        Cellular accumulation of antineoplaston AS2- 1 in human hepatoma cells.
        Cancer Lett. 1995; 88: 107-112
        • Thibault A
        • Samid D
        • Cooper MR
        • Flgg WD
        • Tompklns AC
        • Patronas N
        • et al.
        Phase I study of phenylacetate administered twice daily to patients with cancer.
        Cancer. 1995; 75: 2932-2938
        • Prados MD
        • Spence A
        • Schold C
        • Robbins I
        • Mehta M
        • Berger M
        • et al.
        A phase II trial of phenylacetic acid for recurrent malignant glioma: preliminary report of the North American Brain Tumor Consortium [abstract].
        Program Proc Am Soc Clin Oncol. 1996; 15: 156