Gossypol treatment of recurrent adult malignant gliomas

Gossypol, a polyphenolic compound which depletes cellular energy by inhibit ion of several intracellular dehydrogenases, has been shown to have antipro liferative activity against human glial tumor cell lines in vitro and in nu de 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 t umors which had recurred after radiation therapy. Fifteen patients had glio blastoma, 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 dise ase progression. Two patients had partial response (PR); 4 had stable disea se for 8 weeks or more. One patient maintained a PR with improved KPS for 7 8 weeks. The other had a PR lasting 8 weeks. Toxicity was mild: 2 heavily p retreated patients had mild thrombocytopenia, 5 patients developed hypokale mia, 3 patients developed grade 2 hepatic toxicity and peripheral edema. Go ssypol 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 wit h recurrent glioma. The presumed novel mechanism of action, lack of signifi cant myelosuppression, and activity in patients with advance glioma support further study of gossypol as an antineoplastic agent.