Drugs in R & D

, Volume 4, Issue 2, pp 91–101 | Cite as

Phase II Study of Antineoplaston A10 and AS2-1 in Patients with Recurrent Diffuse Intrinsic Brain Stem Glioma

A Preliminary Report
  • Stanislaw R. BurzynskiEmail author
  • Robert I. Lewy
  • Robert A. Weaver
  • Maxwell L. Axler
  • Tomasz J. Janicki
  • Gabor F. Jurida
  • Jaroslaw K. Paszkowiak
  • Barbara G. Szymkowski
  • Mohammad I. Khan
  • Mark Bestak
Original Research Article


Objective: A phase II study of antineoplaston A10 and AS2-1 was conducted to evaluate the antineoplastic activity in patients with recurrent diffuse intrinsic brain stem glioma.

Patients and methods: This report describes the results of treatment of the first 12 patients admitted to the study. Patients received escalating doses of antineoplaston A10 and AS2-1 by intravenous bolus injections. The median duration of treatment was 6 months and the average dosage of antineoplaston A10 was 11.3 g/kg/day and of antineoplaston AS2-1 0.4 g/kg/day. Responses were assessed by gadolinium-enhanced magnetic resonance imaging of the head.

Results: Of ten evaluable patients, complete response was determined in two cases (20%), partial response in three (30%), stable disease in three (30%) and progressive disease in two (20%). Survival at 2 years was 33.3%. Currently, of all 12 patients, two (17%) were alive and tumour free for over 5 years since initial diagnosis; one was alive for more than 5 years, and another for more than 4 years from the start of treatment. Only mild and moderate toxicities were observed, which included three cases of skin allergy, two cases of anaemia, fever and hypernatraemia, and single cases of agranulocytosis, hypoglycaemia, numbness, tiredness, myalgia and vomiting.

Conclusion: The results of this study compared favourably with the responses of patients treated with radiation therapy and chemotherapy. The study continues with accrual of additional patients.


Proliferate Cell Nuclear Antigen Brain Stem Glioma Phenylacetate Eflornithine Develop Tumour Recurrence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by a grant from California Age Research Institute. Antineoplaston A10 and AS2-1 were given free of charge.

The authors express their appreciation to Dr Dieter Schellinger and Dr Joshua Pleasure for evaluation of MRI films. We acknowledge the contribution of the following local co-investigators: Drs David Bigos, Arie Ashkenasi, Robert Steele, Joan B. Parkhurst, Jordan Wilbur, M.O. Tomeh, Matt W. Hemstreet, Luis A. Rodriguez, Theddore Cole, David Castellan, Chris Arth.


  1. 1.
    Burzynski SR, Kubove E, Burzynski B. Phase II clinical trials of antineoplastons A10 and AS2-1 infusions in astrocytoma. In: Adam D, editor. Recent advances in chemotherapy. Munich: Futramed Publishers, 1992: 2506–7Google Scholar
  2. 2.
    Freeman CR, Farmer JP. Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 1998; 40: 265–71PubMedCrossRefGoogle Scholar
  3. 3.
    Fleming TR. One-sample multiple testing procedure for phase II clinical trials. Biometrics 1982; 38: 143–51PubMedCrossRefGoogle Scholar
  4. 4.
    Adam L, Crépin M, Savin C, et al. Sodium phenylacetate induces growth inhibition and Bcl-2 down-regulation and apoptosis in MCF7 ras cells in vitro and in nude mice. Cancer Res 1995; 55: 5156–60PubMedGoogle Scholar
  5. 5.
    Samid D, Shack S, Sherman LT. Phenylacetate: a novel nontoxic inducer of tumor cell differentiation. Cancer Res 1992; 52: 1988–92PubMedGoogle Scholar
  6. 6.
    Shack S, Chen LC, Miller AC, et al. Increased susceptibility of ras-transformed cells to phenylacetate is associated with inhibition of p21ras isoprenylation and phenotypic reversion. Int J Cancer 1995; 63: 124–9PubMedCrossRefGoogle Scholar
  7. 7.
    DiCroce L, Raker VA, Corsaro M, et al. Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 2002; 295: 1079–82CrossRefGoogle Scholar
  8. 8.
    Gorospe M, Shack S, Guyton KZ, et al. Up-regulation and functional role of p21WAF1/Cip1 during growth arrest of human breast carcinoma MCF-7 cells by phenylacetate. Cell Growth Differ 1996; 7: 1609–15PubMedGoogle Scholar
  9. 9.
    Liu L, Samid D. Mutant p53 as a target of phenylacetate in human glioblastoma [abstract 2580]. Proceedings of the 86th Annual Meeting of the American Association for Cancer Research, Toronto, Canada; AACR 1995, 433 433Google Scholar
  10. 10.
    Kamitani H, Tanjura S, Watanbe K, et al. Histone acetylation may suppress human glioma cell proliferation with p21WAF1/Cip1 and gelsolin are induced. Neuro-Oncol 2002; 4: 95–101PubMedGoogle Scholar
  11. 11.
    Burzynski SR, Mohabbat MO, Lee SS. Preclinical studies of antineoplaston AS2-1 and antineoplaston AS2-5. Drugs Exp Clin Res 1986; 12 (Suppl 1): 11–6PubMedGoogle Scholar
  12. 12.
    Ram Z, Samid D, Waldbridge S, et al. Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate. Cancer Res 1994; 54: 2923–7PubMedGoogle Scholar
  13. 13.
    Stockhammer G, Manley GT, Johnson R, et al. Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate. J Neurosurg 1995; 83: 672–81PubMedCrossRefGoogle Scholar
  14. 14.
    Liu L, Shack S, Stetler-Stevenson WG, et al. Differentiation of cultured human melanoma cells induced by the aromatic fatty acids phenylacetate and phenylbutyrate. J Invest Dermatol 1994; 103: 355–40CrossRefGoogle Scholar
  15. 15.
    Danesi R, Nardini D, Basolo F, et al. 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: 972–9PubMedGoogle Scholar
  16. 16.
    Sidell N, Wada R, Han G, et al. Phenylacetate synergizes with retinoic acid in inducing the differentiation of human neuroblastoma cells. Int J Cancer 1995; 60: 507–14PubMedCrossRefGoogle Scholar
  17. 17.
    Cinatl J, Cinatl JA, Herneiz P, et al. Induction of myogenic differentiation in a human rhabdomyosarcoma cell line by phenylacetate. Cancer Lett 1994; 78: 41–8PubMedCrossRefGoogle Scholar
  18. 18.
    Ferrandina G, Melichar B, Loercher A, et al. Growth inhibitory effects of sodium phenylacetate (NSC 3039) on ovarian carcinoma cells in vitro. Cancer Res 1997; 57: 4309–15PubMedGoogle Scholar
  19. 19.
    Samid D, Yeh A, Prasanna P. Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate. Blood 1992; 809: 1576–81Google Scholar
  20. 20.
    Burzynski SR, Kubove E, Burzynski B. Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1. Drugs Exp Clin Res 1990; 16: 361–9PubMedGoogle Scholar
  21. 21.
    Liau MC, Liau CP, Burzynski SR. Potentiation of induced terminal differentiation by phenylacetic acid and related chemicals. Int J Exp Clin Chemother 1992; 5: 9–17Google Scholar
  22. 22.
    Tsuda H, Hara H, Eriguchi N, et al. Inhibitory effect of antineoplaston A10 on breast cancer transplanted to athymic mice and human hepatocellular carcinoma cell lines. Kurume Med J 1990; 37: 97–104PubMedCrossRefGoogle Scholar
  23. 23.
    Wood JC, Copland JA, Muldoon TG, et al. 3-phenylacetylamino-2, 6-piperidinedione inhibition of rat Nb2 lymphoma cell mitogenesis. Proc Soc Exp Biol Med 1991; 197: 404–8PubMedGoogle Scholar
  24. 24.
    Xu W, Yu R, Gao C, et al. The preliminary antitumor assay of antineoplaston A10 against the s180 and the effects of cAMP levels in tumor and liver tissues of mice. Adv Exp Clin Chemother 1988; 2: 41–4Google Scholar
  25. 25.
    Hashimoto K, Koga T, Shintomi Y, et al. The anticancer effect of antineoplaston A10 on human breast cancer serially transplanted to athymic mice. Nippon Gan Chiryo Gakkai Shi 1990; 25: 1–5PubMedGoogle Scholar
  26. 26.
    Burzynski SR. Purified antineoplaston fractions and methods of treating neoplastic disease. US patent 4,470,970. 1984Google Scholar
  27. 27.
    Burzynski SR. Phase I clinical studies of antineoplaston AS2-5 injections. In: Ishigami J, editor. Recent advances in chemotherapy. Tokyo: University of Tokyo Press, 1985: 586–7Google Scholar
  28. 28.
    Burzynski SR. Potential of antineoplastons in diseases of old age. Drugs Aging 1995; 7: 157–67PubMedCrossRefGoogle Scholar
  29. 29.
    Chang SM, Kuhn JG, Robins HI, et al. Phase II study of phenylacetate in patients with recurrent malignant glioma: a North American Brain Tumor Consortium Report. J Clin Oncol 1999; 17: 984–90PubMedGoogle Scholar
  30. 30.
    Buckner JD, Malkin MG, Reed E, et al. Phase II study of antineoplaston A10 (NSC 648539) and AS2-1 (NSC 6200261) in patients with recurrent glioma. Mayo Clin Proc 1999; 74: 137–45PubMedCrossRefGoogle Scholar
  31. 31.
    Burzynski SR. Efficacy of antineoplastons A10 and AS2-1. Mayo Clin Proc 1999; 74: 641–2PubMedCrossRefGoogle Scholar
  32. 32.
    Fulton DS, Levin VA, Wara WM, et al. Chemotherapy of pediatric brain-stem tumors. J Neurosurg 1981; 54: 721–5PubMedCrossRefGoogle Scholar
  33. 33.
    Rodriguez LA, Prados M, Fulton D, et al. Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Neurosurgery 1988; 23: 691–3CrossRefGoogle Scholar
  34. 34.
    Allen JC, Hancock C, Walker R, et al. PCNU and recurrent childhood brain tumors. J Neurooncol 1987; 5: 241–4PubMedCrossRefGoogle Scholar
  35. 35.
    van Eys J, Baram TZ, Cangir A, et al. Salvage chemotherapy for recurrent primary brain tumors in children. J Pediatr 1988; 113: 601–6PubMedCrossRefGoogle Scholar
  36. 36.
    Prados M, Rodriguez L, Chamberlain M, et al. Treatment of recurrent gliomas with 1, 3-bis(2-chlorethyl)-1-nitrosourea and α-fluromethylornithine. Neurosurgery 1989; 24: 806–9PubMedCrossRefGoogle Scholar
  37. 37.
    Heideman RL, Packer RJ, Reaman GH, et al. A phase II evaluation of thiotepa in pediatric central nervous system malignancies. Cancer 1993; 72: 271–5PubMedCrossRefGoogle Scholar
  38. 38.
    Corden BJ, Strauss LC, Killmond T, et al. Cisplatin, ara-C and etoposide (PAE) in the treatment of recurrent childhood brain tumors. J Neurooncol 1991; 11: 57–63PubMedCrossRefGoogle Scholar
  39. 39.
    Pendergrass TW, Milstein JM, Geyer JR, et al. Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy. J Clin Oncol 1987; 5: 1221–31PubMedGoogle Scholar
  40. 40.
    Mandell LR, Kadota R, Freeman C, et al. There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brain stem tumors: results of pediatric oncology group phase III trial comparing conventional vs hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 1999; 43: 959–64PubMedCrossRefGoogle Scholar
  41. 41.
    Jennings MT, Sposto R, Boyett JM, et al. Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the children’s cancer group. J Clin Oncol 2002; 20 (16): 3431–7PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2003

Authors and Affiliations

  • Stanislaw R. Burzynski
    • 1
    Email author
  • Robert I. Lewy
    • 2
  • Robert A. Weaver
    • 1
  • Maxwell L. Axler
    • 2
  • Tomasz J. Janicki
    • 3
  • Gabor F. Jurida
    • 4
  • Jaroslaw K. Paszkowiak
    • 3
  • Barbara G. Szymkowski
    • 1
  • Mohammad I. Khan
    • 5
  • Mark Bestak
    • 4
  1. 1.Department of Internal MedicineBurzynski ClinicHoustonUSA
  2. 2.Department of Medical OncologyBurzynski ClinicHoustonUSA
  3. 3.Department of Medical Documentation and Data ProcessingBurzynski ClinicHoustonUSA
  4. 4.Department of Pediatric OncologyBurzynski ClinicHoustonUSA
  5. 5.Department of RadiologyBurzynski ClinicHoustonUSA

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