Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma

Endocr Relat Cancer. 2010 Aug 16;17(3):797-807. doi: 10.1677/ERC-09-0341. Print 2010 Sep.

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.

MeSH terms

  • Adrenal Cortex Neoplasms / drug therapy*
  • Adrenal Cortex Neoplasms / metabolism*
  • Adrenal Cortex Neoplasms / mortality
  • Adrenocortical Carcinoma / drug therapy*
  • Adrenocortical Carcinoma / metabolism*
  • Adrenocortical Carcinoma / 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
  • Mitotane / blood
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Mitotane
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin