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Efficacy of Antineoplastons A10 and AS2-1

      To the Editor: I read with interest the article by Buckner et al, in the February 1999 issue of Mayo Clinic Proceedings (pages 137 to 145), on the efficacy of antineoplastons A10 and AS2-1. Although the study results were not conclusive, the study tested a dosing regimen known to be ineffective. Specifically, the dosages of A10 and AS2–1 used in the study were meant for the treatment of a single small lesion (<5 cm). Five of the 6 evaluable patients had either multiple nodules or tumors larger than 5 cm. As the provider of A10 and AS2–1, I strongly suggested to the National Cancer Institute (NCI) that these patients receive a much higher dose, consistent with their greater tumor load. In fact, the study was closed when I insisted that the NCI either increase the dosage or inform the patients that the drug manufacturer believed that the treatment was unlikely to be effective at the dosages being used (letter to Dr M. Sznol, NCI, on April 20, 1995).
      A review of the clinical data in the article by Buckner et al proves the validity of my position. Their study patients had extremely low plasma antineoplaston levels. My phase 2 study dosage regimen produced plasma phenylacetylglutamine levels that are 35 times greater, phenylacetylisoglutamine levels 53 times greater, and phenylacetate levels 2 times greater than those reported by Buckner et a1.

      Burzynski Research Institute, Houston, Tex. Annual Report to FDA: IND 43,742. 1998.

      The clinical outcomes reported by Buckner et al, based on their inadequate dosage schedule, differ dramatically from my phase 2 studies in which a higher dosage regimen was used. They reported no tumor regression. In contrast, in 1 of my ongoing studies on protocol BT-9, 4 of 8 evaluable patients with astrocytoma had objective responses.
      • Burzynski SR
      Antineoplastons in the treatment of malignant brain tumors.
      The difference in outcomes is primarily due to the difference in dosage schedules.
      Another factor that may have caused a lack of response in the study by Buckner et al is that the duration of treatment was too brief. Almost all the patients in their study received treatment for less than 30 days. One patient received only 9 days of treatment. The current studies indicate that objective tumor responses are usually observed after 3 months of therapy. An additional 8 months of treatment is usually needed to obtain a maximal therapeutic effect.
      I also want to point out ambiguities in the response evaluation and analysis in the article by Buckner et al. In 2 patients, tumor necrosis was attributed to “radionecrosis.” However, such an interpretation is clouded by the fact that antineoplaston-induced necrosis can be indistinguishable from radionecrosis. Moreover, the analysis by Buckner et al could have highlighted the 2 patients with recurrent glioblastoma who survived for more than 1 year. This is of interest because these patients typically have a life expectancy of 3 to 6 months.
      It is regrettable that, at the time of the study by Buckner et al, the sponsor, NCI, decided against the higher dosing regimen that I proposed and closed the study. I compliment Buckner et al for their work in evaluating antineoplaston efficacy. It is unfortunate, however, that their study used a dosing regimen known to be ineffective.

      References

      1. Burzynski Research Institute, Houston, Tex. Annual Report to FDA: IND 43,742. 1998.

        • Burzynski SR
        Antineoplastons in the treatment of malignant brain tumors.
        in: Klatz RM Goldman R Anti-Aging Medical Therapeutics. Vol 2. Health Quest Publications, Marina del Rey, Calif1998: 29-34

      Linked Article

      • Efficacy of Antineoplastons A10 and AS2-1: In Response
        Mayo Clinic ProceedingsVol. 74Issue 6
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          Dr Burzynski raises 3 important issues in evaluating treatment outcomes in patients with recurrent gliomas: the relationship between dose and response, the evaluation of objective response, and the meaning of tumor necrosis after both radiation and drug therapy. In our study, we used a gradually escalating dosing scheme over 4 days to the target dosages of 10 g/kg per day for antineoplaston A10 and 0.4 g/kg per day for antineoplaston AS2-1, which resulted in a dosage of 320 mg/kg per day of phenylacetate.
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