Medical treatment of metastatic adrenal cancer is largely unsuccessful and has considerable toxicity. We previously demonstrated the activity of the plant toxin gossypol against human adrenal cancers in nude mice. We therefore examined the efficacy and toxicity of oral gossypol as a treatment for adrenal cancer in humans. Twenty-one patients with metastatic adrenal cancer received oral gossypol at doses of 30-70 mg/day. Patients were monitored for side effects of gossypol, changes in hormone secretion, and tumor response. Eighteen patients completed at least 6 weeks of gossypol treatment. Three of these patients, whose tumors were refractory to other chemotherapeutic agents, had partial tumor responses (> or = 50% decrease in tumor volume) that lasted from several months to over 1 yr. One patient had a minor response followed by resection of her remaining disease, 1 patient had stable disease, and 13 patients had disease progression. Three patients died of their disease without receiving sufficient gossypol to achieve detectable drug levels, and were eliminated from the final analysis. The side effects of gossypol were generally well tolerated; the only serious side effect was abdominal ileus that resolved when the drug was temporarily withheld and restarted at a lower dose. We conclude that oral gossypol can be used relatively safely on an outpatient basis for the treatment of metastatic adrenal cancer. The response rate is similar to the other agents currently available for adrenal cancer, and responses were seen in patients who had failed other chemotherapeutic regimens. This study provides the first indication that gossypol may have activity against cancer in humans, suggesting the need for further investigation of gossypol as an antitumor agent.

Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.

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