Adrenocortical carcinoma (ACC) is a rare malignancy and most of the therapeutic strategies are not yet prospectively validated. However, several studies have been published in 2010 and preliminary results from two prospective trials are available now.
Open adrenalectomy is treatment of choice for resectable tumors. However, two recent retrospective studies provided evidence that a laparoscopic approach might be also a safe alternative in selected cases (especially in tumors preoperatively of uncertain malignancy). Based on a study by Terzolo et al. (NEJM 2007), adjuvant mitotane treatment is recommended for the majority of patients. However, prospective data suggest that the outcome in patients with stage II ACC is better as assumed in the past. Therefore, prospective trials like the currently running randomized ADIUVO trial on adjuvant mitotane are urgently needed.
In advanced ACC, the first ever randomised trial (FIRM-ACT study) will set the new standard in first-line cytotoxic therapy. Preliminary results showed a clear trend for improved overall survival by the combination of etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) in comparison to streptocotozin and mitotane (14.8 vs 12.0 months; P=0.069) and progression-free survival was clearly prolonged by EDP-M (5.7 vs 2.1 months; P<0.0001). The first experience using targeted therapies is disappointing: gefitinib, sorafenib, erlotinib+gemcitabine, or bevacizumab+capecitabine exhibited only limited efficacy in pretreated patients. An interesting observation was found in the SIRAC study investigating sunitinib in refractory ACC. The preliminary analysis indicated that in 5 of 35 evaluable patients (15.3%) a prolonged stable disease for >12 weeks was seen. Of note, concomitant mitotane did rather impair the clinical outcome, which might be related to an induction of CYP3A4 enzyme. Another important study investigating the efficacy of the IGF1 receptor inhibitor OSI-906 in a placebo controlled phase III trial, is currently still recruiting.
Overall the prognosis of ACC is still poor and 5-year survival rate is about 45%. However, recent collaborative efforts (e.g. by the European adrenal network ENSAT) and ongoing international trials will further advance the field in the near future.
30 Apr - 04 May 2011
European Society of Endocrinology