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Gossypol Treatment of Recurrent Adult Malignant Gliomas

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Abstract

Gossypol, a polyphenolic compound which depletes cellular energy by inhibition of several intracellular dehydrogenases, has been shown to have antiproliferative activity against human glial tumor cell lines in vitro and in nude mouse xenografts. Human trials of gossypol as a male contraceptive have demonstrated safety of long-term administration. We studied the activity of Gossypol 10 mg PO bid in 27 patients with pathologically confirmed glial tumors which had recurred after radiation therapy. Fifteen patients had glioblastoma, 11 patients anaplastic astrocytoma, 1 patient relapsed low grade glioma. Response was assessed every 8 weeks using CT/MRI scan and clinical criteria including decadron requirement. Treatment was continued until disease progression. Two patients had partial response (PR); 4 had stable disease for 8 weeks or more. One patient maintained a PR with improved KPS for 78 weeks. The other had a PR lasting 8 weeks. Toxicity was mild: 2 heavily pretreated patients had mild thrombocytopenia, 5 patients developed hypokalemia, 3 patients developed grade 2 hepatic toxicity and peripheral edema. Gossypol levels measured by HPLC did not correlate with response or toxicity in this study.

We conclude that gossypol is well tolerated and has a low, but measurable, response rate in a heavily pretreated, poor-prognosis group of patients with recurrent glioma. The presumed novel mechanism of action, lack of significant myelosuppression, and activity in patients with advance glioma support further study of gossypol as an antineoplastic agent.

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Authors and Affiliations

  1. Department of Medicine and University of Rochester Cancer Center, University of Rochester, Rochester, NY, USA

    Peter Bushunow

  2. Departments of Pharmacology and Medicine, Cornell University Medical College, NY, New York, USA

    Marcus M. Reidenberg & Beverly Lorenzo

  3. Department of Radiology, SUNY Health Science Center, Syracuse, NY, USA

    John Wasenko

  4. Department of Neurosurgery, SUNY Health Science Center, Syracuse, NY, USA

    Jeffrey Winfield & Thomas Coyle

  5. Department of Medicine, SUNY Health Science Center, Syracuse, NY, USA

    Sheila Lemke, Benjamin Himpler & Thomas Coyle

  6. Department of Pathology, SUNY Health Science Center, Syracuse, NY, USA

    Robert Corona

Authors
  1. Peter Bushunow
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  2. Marcus M. Reidenberg
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  3. John Wasenko
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  4. Jeffrey Winfield
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  5. Beverly Lorenzo
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  6. Sheila Lemke
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  7. Benjamin Himpler
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  8. Robert Corona
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  9. Thomas Coyle
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Bushunow, P., Reidenberg, M.M., Wasenko, J. et al. Gossypol Treatment of Recurrent Adult Malignant Gliomas. J Neurooncol 43, 79–86 (1999). https://doi.org/10.1023/A:1006267902186

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