TY - JOUR
T1 - Plasma concentrations of o,p′DDD, o,p′DDA, and o,p′DDE as predictors of tumor response to mitotane in adrenocortical carcinoma
T2 - Results of a retrospective ENS@T multicenter study
AU - Hermsen, Ilse G.
AU - Fassnacht, Martin
AU - Terzolo, Massimo
AU - Houterman, Saskia
AU - Den Hartigh, Jan
AU - Leboulleux, Sophie
AU - Daffara, Fulvia
AU - Berruti, Alfredo
AU - Chadarevian, Rita
AU - Schlumberger, Martin
AU - Allolio, Bruno
AU - Haak, Harm R.
AU - Baudin, Eric
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Context: In patients with adrenocortical carcinoma (ACC) mitotane activity has been suggested to depend on plasma levels 14mg/liter or greater and metabolite formation. Objective: The study was performed to confirm the correlation of the currently used mitotane (o,p′DDD) threshold of 14 mg/liter with tumor response and to evaluate the additional value of 1,1-(o,p′-dichlorodiphenyl) acetic acid (o,p′DDA) and o,p′DDE (1,1-(o,p′-dichlorodiphenyl)-2,2 dichloroethene) levels for predicting tumor response. Subjects/Methods: Plasma samples collected within 3 months of best response from 91 patients on mitotane therapy for advanced ACC were analyzed retrospectively. O,p′DDD and metabolites were assessed and related to tumor response and survival. Receiver operating characteristic curves were used. Sensitivity and specificity were calculated for different cutoff levels of o,p′DDD and metabolites. Results: Objective tumor response was observed in 19% of patients. Median o,p′DDD level was higher in responders (P = 0.03). More responders were found among patients achieving o,p′DDD levels 14 mg/liter or greater (P = 0.02). Univariate and multivariate analysis showed significantly longer survival for patients with o,p′DDD levels 14 mg/liter or greater (hazard ratio 0.52, P = 0.04, hazard ratio 0.46, P = 0.03). An o,p′DDD cutoff value of 14 mg/liter was associated with a sensitivity of 65% and specificity 69%. An o,p′DDD level 20 mg/liter or greater or 14 mg/liter or greater combined with o,p′DDA level 92 mg/liter or greater was associated with a specificity of 90 and 92%, respectively. Conclusions: Our data confirm the value of o,p′DDD plasma monitoring as well as targeting the 14 mg/liter cutoff level in the therapeutic management of ACC patients. Furthermore, our results suggest additional benefit of higher levels of o,p′DDD and combined measurement of o,p′DDD and o,p′DDA.
AB - Context: In patients with adrenocortical carcinoma (ACC) mitotane activity has been suggested to depend on plasma levels 14mg/liter or greater and metabolite formation. Objective: The study was performed to confirm the correlation of the currently used mitotane (o,p′DDD) threshold of 14 mg/liter with tumor response and to evaluate the additional value of 1,1-(o,p′-dichlorodiphenyl) acetic acid (o,p′DDA) and o,p′DDE (1,1-(o,p′-dichlorodiphenyl)-2,2 dichloroethene) levels for predicting tumor response. Subjects/Methods: Plasma samples collected within 3 months of best response from 91 patients on mitotane therapy for advanced ACC were analyzed retrospectively. O,p′DDD and metabolites were assessed and related to tumor response and survival. Receiver operating characteristic curves were used. Sensitivity and specificity were calculated for different cutoff levels of o,p′DDD and metabolites. Results: Objective tumor response was observed in 19% of patients. Median o,p′DDD level was higher in responders (P = 0.03). More responders were found among patients achieving o,p′DDD levels 14 mg/liter or greater (P = 0.02). Univariate and multivariate analysis showed significantly longer survival for patients with o,p′DDD levels 14 mg/liter or greater (hazard ratio 0.52, P = 0.04, hazard ratio 0.46, P = 0.03). An o,p′DDD cutoff value of 14 mg/liter was associated with a sensitivity of 65% and specificity 69%. An o,p′DDD level 20 mg/liter or greater or 14 mg/liter or greater combined with o,p′DDA level 92 mg/liter or greater was associated with a specificity of 90 and 92%, respectively. Conclusions: Our data confirm the value of o,p′DDD plasma monitoring as well as targeting the 14 mg/liter cutoff level in the therapeutic management of ACC patients. Furthermore, our results suggest additional benefit of higher levels of o,p′DDD and combined measurement of o,p′DDD and o,p′DDA.
UR - http://www.scopus.com/inward/record.url?scp=79956306619&partnerID=8YFLogxK
U2 - 10.1210/jc.2010-2676
DO - 10.1210/jc.2010-2676
M3 - Article
C2 - 21470991
AN - SCOPUS:79956306619
SN - 0021-972X
VL - 96
SP - 1844
EP - 1851
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -