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

Abstract

Context: Mitotane 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.

Objective: To compare recurrence-free survival (RFS) in patients who reached and maintained mitotane concentrations ≥ 1 4 mg/l vs patients who did not.

Design and setting: Retrospective analysis at six referral European centers.

Patients: Patients 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 measures: RFS (primary) and overall survival (secondary).

Results: Of 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.

Conclusions: Mitotane 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.