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Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma
Endocr Relat Cancer
1479-6821 (Electronic)1351-0088 (Linking)
Malandrino, PasqualinoAl Ghuzlan, AbirCastaing, MarineYoung, JacquesCaillou, BernardTravagli, Jean-PaulElias, Dominiquede Baere, ThierryDromain, ClarissePaci, AngeloChanson, PhilippeSchlumberger, MartinLeboulleux, SophieBaudin, EricengEngland2010/07/02 06:00Endocr Relat Cancer. 2010 Aug 16;17(3):797-807. doi: 10.1677/ERC-09-0341. Print 2010 Sep.
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.
Adrenal Cortex Neoplasms/*drug therapy/*metabolism/mortality, Adrenocortical Carcinoma/*drug therapy/*metabolism/mortality, Adult, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Biomarkers, Tumor/*metabolism, Cisplatin/administration & dosage, DNA-Binding Proteins/metabolism, Endonucleases/metabolism, Female, Humans, Lymphatic Metastasis, Male, Middle Aged, Mitotane/administration & dosage/blood, Prognosis, Prospective Studies, Retrospective Studies, Survival Rate, Treatment Outcome
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