We have demonstrated that adjuvant mitotane prolong recurrence free survival (RFS) in patients with radically resected ACC. Aim of the present study was to correlate mitotane levels with patient outcome in an adjuvant setting in 3 different referral centres in Europe. There were 120 patients (45 W, 75 M, median age 44 years, range 1676) radically resected for ACC who were treated adjuvantly with mitotane from 1996 to 2010. ACC was stage I in 10 cases, II in 73, III in 31, IV in 6; 62 patients had secreting ACC. Forty patients were treated with 810 g/daily and 80 patients with 16 g/daily. Target mitotane concentrations of 1420 mg/l were attained within 3 months from treatment start in 49 patients (41%), within 6 months in additional 61 patients (51%), while 10 patients (8%) never got them. Mitotane levels >14 mg/l were maintained in more than 75% of determinations in 64 patients (53%). Median duration of treatment was 25.5 months (range: 4165) and median duration of follow-up was 36 months (6165). Only 11 patients (9%) experienced severe adverse events (CTC 3), but none of the patients discontinued mitotane definitively for toxicity. At the last follow-up, 58 patients (48%) relapsed and 33 patients (27%) died. RFS was significantly longer in patients who attained target mitotane concentrations within 3 months (P=0.01) and in patients who maintained consistently levels >14 mg/l during follow-up (P=0.004). In a multivariate analysis (including sex, age, stage, number of mitoses or Ki-67 value) maintenance of target mitotane concentrations was an independent factor influencing RFS (HR=0.41, 95%CI 0.210.77; P=0.006). The effect on overall survival was significant only in univariate but not in multivariate analysis (HR=0.61, 0.261.43). The present data demonstrate for the first time that target mitotane concentrations may have a therapeutic impact in an adjuvant setting. This finding supports indirectly the efficacy of adjuvant mitotane treatment.
30 Apr - 04 May 2011
European Society of Endocrinology