title: Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma.
abstract: To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level > or =14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.
authors.affiliation: Service de Médecine Nucléaire et de Cancérologie Endocrinienne, Institut Gustave-Roussy, Université Paris XI, 39 rue Camille Desmoulins, Villejuif Cedex, France.
authors.forename: Pasqualino
authors.initials: P
authors.lastname: Malandrino
authors.forename: Abir
authors.initials: A
authors.lastname: Al Ghuzlan
authors.forename: Marine
authors.initials: M
authors.lastname: Castaing
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Bernard
authors.initials: B
authors.lastname: Caillou
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Travagli
authors.forename: Dominique
authors.initials: D
authors.lastname: Elias
authors.forename: Thierry
authors.initials: T
authors.lastname: de Baere
authors.forename: Clarisse
authors.initials: C
authors.lastname: Dromain
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Sophie
authors.initials: S
authors.lastname: Leboulleux
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000008:administration & dosage / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D008939:Mitotane; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin