Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma

摘要: Summary Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, (o,p’-DDD)] is the only drug approved for treatment adrenocortical carcinoma (ACC) and has also been used various forms of glucocorticoid excess. Through still largely unknown mechanisms, mitotane inhibits adrenal steroid synthesis cell proliferation. Mitotane increases hepatic metabolism cortisol, an increased replacement dose glucocorticoids standard care during treatment. Recently, sunitinib, a multityrosine kinase inhibitor (TKI), found to be rapidly metabolized by CYP3A4 treatment, indicating clinically relevant interactions with mitotane. We here summarize current evidence concerning mitotane-induced changes in monooxygenase expression, list drugs potentially affected mitotane-related induction suggest alternatives. For example, using doses macrolide antibiotics unlikely reach sufficient plasma levels, making fluoroquinolones many cases superior choice. Similarly, statins such as simvastatin are CYP3A4, whereas others like pravastatin not. Importantly, past, several clinical trials cytotoxic but targeted therapies ACC yielded disappointing results. This lack antineoplastic activity may explained part insufficient exposure owing enhanced induced Thus, needs considered design future ACC.