Context: Mitotane plasma concentrations ≥ 14 mg/l have been shown to predict tumor response and better survival in patients with advanced adrenocortical cancer (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 ≥ 14 mg/l versus patients who did not.
Design and Setting: Retrospective analysis at 6 referral European centers.
Patients: Patients with ACC who were radically resected between 1999 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 multivariate analysis, the maintenance of target mitotane concentrations was associated with a significantly prolonged RFS (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). Grade 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.
Written by:
Terzolo M, Baudin E, Ardito A, Kroiss M, Leboulleux S, Daffara F, Perotti P, Feelders RA, Devries JH, Zaggia B, De Francia S, Volante M, Haak HR, Allolio B, Al Ghuzlan A, Fassnacht M, Berruti A. Are you the author?
M Terzolo, Department of Clinical and Biological Science, Internal Medicine I, Orbassano, Italy.
Reference: Eur J Endocrinol. 2013 May 23. Epub ahead of print.
doi: 10.1530/EJE-13-0242
PubMed Abstract
PMID: 23704714
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