Cottonseed [gossypol] for treatment of glioma [brain tumor]

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harold jitschak bueno de mesquita

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Jun 7, 2009, 2:27:05 AM6/7/09
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............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.





Peter Bushunow1, Marcus M. Reidenberg2, John Wasenko3, Jeffrey Winfield4, Beverly Lorenzo2, Sheila Lemke5, Benjamin Himpler5, Robert Corona6 and Thomas Coyle4, 5

(1)  Department of Medicine and University of Rochester Cancer Center, University of Rochester, Rochester, NY, USA
(2)  Departments of Pharmacology and Medicine, Cornell University Medical College, NY, New York, USA
(3)  Department of Radiology, SUNY Health Science Center, Syracuse, NY, USA
(4)  Department of Neurosurgery, SUNY Health Science Center, Syracuse, NY, USA
(5)  Department of Medicine, SUNY Health Science Center, Syracuse, NY, USA
(6)  Department of Pathology, SUNY Health Science Center, Syracuse, NY, USA

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 10thinspmg 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





prpglioma prpglioblastoma prpcottonseed

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