Conventional and novel strategies in the treatment of adrenocortical cancer

Adrenocortical carcinoma is a highly malignant neoplasm with an incidence o f two per million people per year. Several treatment strategies have result ed in temporary or partial tumor regression but very few cases have attaine d long survival. Surgical resection of the primary tumor and metastases is most effective. Several chemotherapeutic protocols have been employed with variable success. Mitotane (o,p'-DDD) is an adrenalytic drug effective in i nducing a tumor response in 33% of patients treated. Mitotane requires meta bolic transformation for therapeutic action. Tumors may vary in their abili ty to metabolize mitotane and the ability of tumors to transform mitotane m ay predict the clinical response to the drug. Preliminary data show a possi ble correlation between metabolic activity of neoplastic adrenocortical tis sue and response to mitotane. We have attempted to develop mitotane analogs with enhanced adrenalytic effect. Compared to mitotane, a di-chloro compou nd, the bromo-chloro and di-bromo analogs appear to have a greater effect. Future approaches to the treatment of adrenocortical carcinoma are likely t o be based on blocking or reversing the biological mechanisms of tumorigene sis. Angiogenic and chemotactic mechanisms may play a role in adrenal tumor growth and inhibition of these mechanisms may result in inhibition of tumo r growth. New mitotane analogs with greater adrenalytic potential could be a promising approach to developing more effective and selective therapies f or adrenal cancer. Alternative approaches should attempt to suppress tumor growth by means of compounds with anti-angiogenic and anti-chemotactic acti vity.