ACC is a rare, heterogeneous malignancy with poor prognosis. Data from the German ACC Registry (n=478) indicate a 5-year survival rate of 47%. In addition to mitotane, cytotoxic drugs are standard of care in advanced ACC. The best results have been reported by Berruti et al. for the combination of mitotane with etoposide, doxorubicin and cisplatin with an objective tumor response rate of 49% in 72 patients. A response rate of 36% was published for the combination of mitotane and streptozotocin in 22 patients. Currently these two most promising regimens are compared in the first ever phase III trial (www.firm-act.org). Up to Dec 2008, 238 patients have been randomized and results will be available in 2011. The first experience using target therapies for ACC was disappointing. The EGFR inhibitor gefitinib, erlotinib (EGFR inhibitor)+gemcitabine or bevacizumab (VEGF antibody)+capecitabine exhibited only limited efficacy. However, trials testing IGF-1 receptor inhibitors or multityrosine kinase inhibitors like sunitinib or sorafinib are ongoing and will hopefully hold more promise.
The role of radiotherapy is not well defined and in the past some authors judged ACC as radio-resistant. By reviewing the literature we could identify ten articles covering radiotherapy in a total of 129 patients (64 postoperative and 65 palliative irradiations). In addition, we analyzed 26 patients receiving palliative radiotherapy from the German ACC Registry. In an adjuvant setting radiotherapy was able to prevent local recurrence in most patients. In advanced disease, response to radiotherapy was seen in 57% of patients. Therefore, ACC is not resistant to radiotherapy, but prospective investigations are needed to fully define its therapeutic potential.
Therefore, further cooperative efforts including well designed clinical trials are needed to improve outcome in patients with ACC.