Mitotane monotherapy in patients with advanced adrenocortical carcinoma

Felix Megerle, Cristina Ronchi, Wiebke Herrman, Wiebke Schloetelburg, Alina Pulzer, Marcus Quinkler, Felix Beuschlein, Stefanie Hahner, Matthias Kroiss, Martin Fassnacht

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Context: While mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease is still scarce.

Objective: To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors

Design/Setting: Multicenter cohort study of three German referral centers.

Patients: 127 patients with advanced ACC treated with mitotane monotherapy.

Outcome measures: RECIST evaluation. Progression-free and overall survival (PFS, OS) by Kaplan-Meier method. Predictive factors by Cox-regression.

Results: Twenty-six patients (20.5%) experienced objective response including three with complete remission. Overall, median PFS was 4.1 months (range 1.0-73) and median OS 18.5 months (range 1.3–220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions): hazard ratio (HR) for progression of 0.51(p=0.002) and for death of 0.59(p=0.017), and initiation of mitotane at delayed advanced recurrence: HR 0.35(p<0.001) and 0.34(p<0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/l had significantly better OS (HR 0.42; p=0.003).

Conclusions: With 20.5% the objective response rate was slightly lower than previously reported. However, more than 20% of patients experienced a long-term disease control >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane andcytotoxic drugs.
Original languageEnglish
Pages (from-to)1686-1695
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
Early online date14 Feb 2018
Publication statusPublished - 1 Apr 2018


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