title: Plasma concentrations of o,p'DDD, o,p'DDA, and o,p'DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: results of a retrospective ENS@T multicenter study.
abstract: BACKGROUND
  In patients with adrenocortical carcinoma (ACC) mitotane activity has been suggested to depend on plasma levels 14 mg/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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, Máxima Medical Centre, P.O. Box 90052, 5600 PD Eindhoven, The Netherlands. i.hermsen@mmc.nl
authors.forename: Ilse G
authors.initials: IG
authors.lastname: Hermsen
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.forename: Saskia
authors.initials: S
authors.lastname: Houterman
authors.forename: Jan
authors.initials: J
authors.lastname: den Hartigh
authors.forename: Sophie
authors.initials: S
authors.lastname: Leboulleux
authors.forename: Fulvia
authors.initials: F
authors.lastname: Daffara
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.forename: Rita
authors.initials: R
authors.lastname: Chadarevian
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Harm R
authors.initials: HR
authors.lastname: Haak
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood* / Q000188:drug therapy; D018268:Adrenocortical Carcinoma / Q000097:blood* / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D018931:Antineoplastic Agents, Hormonal; C054917:2,2-(2-chlorophenyl-4'-chlorophenyl)acetic acid; D008939:Mitotane; C054919:2,2-(2-chlorophenyl-4'-chlorophenyl)-1,1-dichloroethene