Context: Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce.
Objective: To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors.
Design and setting: Multicenter cohort study of three German referral centers.
Patients: One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy.
Outcome measures: Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and 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 to 73) and median OS 18.5 months (range 1.3 to 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 longer OS (HR 0.42; P = 0.003).
Conclusions: At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >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 and cytotoxic drugs.
Trial registration: ClinicalTrials.gov NCT00453674.