Article

Journal of Neuro-Oncology

, Volume 43, Issue 1, pp 79-86

First online:

Gossypol Treatment of Recurrent Adult Malignant Gliomas

  • Peter BushunowAffiliated withDepartment of Medicine and University of Rochester Cancer Center, University of Rochester
  • , Marcus M. ReidenbergAffiliated withDepartments of Pharmacology and Medicine, Cornell University Medical College
  • , John WasenkoAffiliated withDepartment of Radiology, SUNY Health Science Center
  • , Jeffrey WinfieldAffiliated withDepartment of Neurosurgery, SUNY Health Science Center
  • , Beverly LorenzoAffiliated withDepartments of Pharmacology and Medicine, Cornell University Medical College
  • , Sheila LemkeAffiliated withDepartment of Medicine, SUNY Health Science Center
  • , Benjamin HimplerAffiliated withDepartment of Medicine, SUNY Health Science Center
  • , Robert CoronaAffiliated withDepartment of Pathology, SUNY Health Science Center
  • , Thomas CoyleAffiliated withDepartment of Neurosurgery, SUNY Health Science CenterDepartment of Medicine, SUNY Health Science Center

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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.

malignant glioma gossypol lactate dehydrogenase isoenzymes chemotherapy