Serum concentration of o,pDDD (mitotane), o,pDDA and o,pDDE as predictors of tumour response in adrenocortical carcinoma: results of a retrospective European Network for the Study of Adrenal Tumors (ENS@T) multicentre study
Ilse Hermsen1, Martin Fassnacht2, Massimo Terzolo3, Saskia Houterman4, Jan den Hartigh5, Sophie Leboulleux6, Fulvia Daffara3, Bruno Allolio2, Alfredo Berruti3, Rita Chadarevian7, Harm Haak1 & Eric Baudin6
Introduction: O,pDDD is the drug of choice for patients with adrenocortical carcinoma (ACC). Monitoring o,pDDD serum level has been proposed as predictor of tumour response. Measurement of o,pDDD metabolites involved in the active pathway may provide an improved prediction of o,pDDD activity. The objective of our study was to (1)to confirm the currently used threshold o,pDDD serum level of 14mg/l for achieving a tumour response and (2)compare the value of o,pDDD, o,pDDA, or o,pDDE levels in predicting tumour response.
Methods: Retrospectively o,pDDD and its metabolites were measured in available samples from 91 patients with advanced ACC in 5 ENS@T centres. Samples within 3 months of best response were used for analyses. ROC curves were used to define cut-off values.
Results: Mitotane was given as monotherapy (30%) or in combination with chemotherapy (70%). Tumour response was observed in 17 patients (19%). Metabolites o,pDDE and o,pDDA showed significant correlation with o,pDDD. Using cut-off value of 14 mg/l for o,pDDD, 11 out of 36 patients (31%) reaching o,pDDD levels >14 mgl were responders compared to only 11% responders in patients with levels <14 mg/l (P=0.02). With o,pDDD cut-off level of >18 mg/l, 5 patients were responders. Using a cut-off value of 92 mg/l for o,pDDA, 6 out of 16 patients (38%) were responders above this level against 15% (11/75) below that level (P=0.03).
Conclusion: Our data confirm that serum concentrations of o,pDDD, and also o,pDDA correlate with response in patients with advanced ACC. The ideal o,pDDD target level might be higher than 14 mg/l.