Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer

Eight patients with adrenocortical cancer were treated with low doses of mi totane (2-3 g daily) while monitoring drug plasma levels. When the mitotane concentrations reached the therapeutic range (defined as mitotane plasma l evels between 14-20 mu g/mL), a dose reduction was performed to avoid toxic ity. Thereafter, the mitotane dose was tailored according to plasma levels. A progressive increase in plasma mitotane concentrations was observed duri ng treatment, and a highly significant linear correlation was found between plasma drug levels and the total mitotane dose. The therapeutic threshold was reached in all patients after 3-5 months and a total mitotane dose 283- 387 g/days (median, 363). The duration of treatment was 8-40 months (median , 9). Toxicity was manageable in all but one patient, who discontinued trea tment. It is therefore possible to design a standard low dose schedule, e.g . 3 g/daily for about 3-4 months with following dose adjustments guided by the monitoring of plasma mitotane levels. This approach is able to provide therapeutic mitotane concentrations and limit the unwanted effects. The pre sent data provide a rationale to change the approach to mitotane treatment in patients with adrenocortical carcinoma from high dose to low dose regime ns.