Endocrine Abstracts (2010) 22 P424

Serum concentration of o,p'DDD (mitotane), o,p'DDA and o,p'DDE 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

1Department of Internal Medicine, Máxima Medical Centre, Eindhoven, Netherlands; 2University of Würzburg, Würzburg, Germany; 3Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; 4MMC Academy, Máxima Medical Centre, Veldhoven, Netherlands; 5Department of Clinical Pharmacy and Toxicology University Medical Centre Leiden, Leiden, Netherlands; 6Department of Nuclear Medicine and Endocrine Oncology, Institute Gustave-Roussy, Villejuif, Villejuif, France; 7HRA-Pharma Paris, Paris, France.

Introduction: O,p’DDD is the drug of choice for patients with adrenocortical carcinoma (ACC). Monitoring o,p’DDD serum level has been proposed as predictor of tumour response. Measurement of o,p’DDD metabolites involved in the active pathway may provide an improved prediction of o,p’DDD activity. The objective of our study was to (1)to confirm the currently used threshold o,p’DDD serum level of 14mg/l for achieving a tumour response and (2)compare the value of o,p’DDD, o,p’DDA, or o,p’DDE levels in predicting tumour response.

Methods: Retrospectively o,p’DDD 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,p’DDE and o,p’DDA showed significant correlation with o,p’DDD. Using cut-off value of 14 mg/l for o,p’DDD, 11 out of 36 patients (31%) reaching o,p’DDD levels >14 mgl were responders compared to only 11% responders in patients with levels <14 mg/l (P=0.02). With o,p’DDD cut-off level of >18 mg/l, 5 patients were responders. Using a cut-off value of 92 mg/l for o,p’DDA, 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,p’DDD, and also o,p’DDA correlate with response in patients with advanced ACC. The ideal o,p’DDD target level might be higher than 14 mg/l.