No evidence for relevant QT interval prolongation in mitotane-treated patients with adrenocortical carcinoma

We designed a single-center retrospective study to assess the QT interval duration and to describe cardio vascular events among patients treated with mitotane for a adrenocortical carcinoma (ACC).

We selected 14 patients (6 males and 8 females) that met the following criteria: ACC treated with mitotane, for whom an electrocardiogram (ECG) at baseline (before mitotane initiation) was available and for whom at least one ECG was available during the course of mitotane therapy together with a concomitant mitotane plasma level determination.

Mean mitotane plasma level at baseline and after treatment showed a significant increase (mean level increased from 0 to 14.9±2 mg/l). At baseline and before mitotane was initiated all QTc intervals were <450 msec for men and <460 msec for women. During the treatment phase with mitotane, no QTc>470 msec was found in any patients respectively for men and women. In addition, no patient showed any significant QTc prolongation (>5% or >10 msec) at any time during mitotane treatment. During a mean follow-up of 15.9±3.5 months (range 2-45 months). No cardiovascular deaths or hospitalization for cardiovascular events was documented. No torsades de pointes were documented on ECG. No syncope, dizziness, heart failure were observed during follow up. Six out of 14 patients died during the follow-up, in five cases due to the progression of the disease, one patient died suddenly at home during followup.

This short and retrospective series shows no evidence that mitotane induce any QT prolongation, even when plasma levels are well above the therapeutic window.