Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection

Abstract

ContextMitotane plasma concentrations ≥14 mg/l have been shown to predict tumor response and better survival in patients with advanced adrenocortical carcinoma (ACC). A correlation between mitotane concentrations and patient outcome has not been demonstrated in an adjuvant setting.ObjectiveTo compare recurrence-free survival (RFS) in patients who reached and maintained mitotane concentrations ≥14 mg/l vs patients who did not.Design and settingRetrospective analysis at six referral European centers.PatientsPatients with ACC who were radically resected between 1995 and 2009 and were treated adjuvantly with mitotane targeting concentrations of 14–20 mg/l.Main outcome measuresRFS (primary) and overall survival (secondary).ResultsOf the 122 patients included, 63 patients (52%) reached and maintained during a median follow-up of 36 months the target mitotane concentrations (group 1) and 59 patients (48%) did not (group 2). ACC recurrence was observed in 22 patients of group 1 (35%) and 36 patients in group 2 (61%). In multivariable analysis, the maintenance of target mitotane concentrations was associated with a significantly prolonged RFS (hazard ratio (HR) of recurrence: 0.418, 0.22–0.79; P=0.007), while the risk of death was not significantly altered (HR: 0.59, 0.26–1.34; P=0.20). Grades 3–4 toxicity was observed in 11 patients (9%) and was managed with temporary mitotane discontinuation. None of the patients discontinued mitotane definitively for toxicity.ConclusionsMitotane concentrations ≥14 mg/l predict response to adjuvant treatment being associated with a prolonged RFS. A monitored adjuvant mitotane treatment may benefit patients after radical removal of ACC.