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This is a combination chemotherapy regimen consisting of four drugs—etoposide, doxorubicin, cisplatin (collectively known as EDP), and mitotane—primarily used in the treatment of advanced or metastatic adrenocortical carcinoma (ACC). The regimen is typically administered intravenously for the cytotoxic agents (etoposide, doxorubicin, cisplatin) and orally for mitotane. Etoposide inhibits topoisomerase II leading to DNA strand breaks; doxorubicin intercalates into DNA and also inhibits topoisomerase II; cisplatin forms DNA crosslinks causing apoptosis; and mitotane selectively destroys adrenocortical cells and may modulate multidrug resistance by interfering with P-glycoprotein. This combination has demonstrated significant activity in ACC with response rates around 48–54% in phase II trials. Mitotane is continued throughout treatment to maintain therapeutic plasma levels. The regimen is associated with hematologic toxicity (notably leukopenia), gastrointestinal side effects from mitotane, nephrotoxicity from cisplatin, cardiotoxicity from doxorubicin, and other class-specific toxicities[1][2][4][6].
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