Endocrine Abstracts

Background: Adrenocortical carcinoma (ACC) is a rare solid tumor with poor prognosis in advanced stages. The adrenolytic drug mitotane and cytotoxic chemotherapies are current treatment options with limited clinical efficacy. Animal experiments pointed to an adrenotoxic effect of sunitinib suggesting potential antineoplastic activity in ACC.

Study population: Thirty-eight patients with advanced ACC progressing after mitotane and 1–3 cytotoxic chemotherapies were included. Mitotane treatment was ongoing in 20 patients.

Primary endpoint: Response defined as progression free survival of ≥12 weeks.

Results: Three patients were unevaluable for response due to withdrawal of consent, noncompliance with the study procedures or a serious adverse event. Of the 35 patients analyzed for response, 5 patients (14%) experienced stable disease (median time to progression 5.8 months, range 5.6–11.2), 24 had progressive disease according to RECIST criteria and 6 patients died of the disease before the first evaluation. Median time to progression was 2.8 months (0.3–5.7). In total, 36 serious adverse events were recorded of which 10 were possibly treatment related. Only 41 treatment-related adverse events were documented (mostly CTC grade 1+2). Surprisingly, the response rate was higher in patients not receiving mitotane (4 out of 15 vs 1 out of 20) suggesting that concomitant mitotane treatment may negatively affect clinical outcome (HR for progressive disease 6.9 (95% CI 0.7–69.9). Therefore, we hypothesize that mitotane may lead to decreased sunitinib plasma concentrations, probably by induction of metabolizing enzymes. This could also explain the low frequency of adverse events which was much lower than expected from other sunitinib trials.

Conclusion: Sunitinib has a modest single-agent activity in ACC. Drug interaction with mitotane may abrogate a more impressive anti-tumor effect of sunitinib. Therefore, a clinical trial of sunitinib in mitotane naïve patients might be warranted.