Abstract 2709: Peritoneal carcinomatosis from ovarian cancer: tissue markers as predictors of response to chemotherapy

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Epithelial ovarian cancers represent 80 to 90% of all ovarian malignancies and are the most common cause of death from gynecological tumors in the Western world. The absence of specific symptoms in the early stages of disease means that around two-thirds of patients are initially diagnosed with advanced disease and/or peritoneal dissemination. Although standard primary treatment now exists for advanced ovarian cancer, there is still no single accepted therapeutic strategy for those who develop recurrent intra-abdominal disease more than 6 months after a complete response. The present study aimed to identify a panel of genes whose expression is correlated with sensitivity or resistance to platinum compounds. Material and methods: Fresh surgical biopsy specimens were obtained from 22 patients with advanced epithelial ovarian cancer during intra-abdominal cytoreductive surgery. Expression levels of ERCC1, GSTP1, MGMT, XPD, BRCA1 were determined by Real Time RT-PCR. Relative gene expression was quantified according to the comparative threshold cycle method (2-ΔΔCτ) using β2-microglobulin and HPRT as endogenous controls and commercial RNA controls derived from normal ovarian tissue mRNA as calibrators. The correlation between pre- and post-surgery expression levels of these markers and response to platinum treatment was examined. Results: Time to progression (TTP) was calculated from the first day of treatment to the date on which objective disease progression was first documented, or death in the absence of progressive disease. At univariate analysis, estimated hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated using the Cox proportional hazard model. In particular, the risk of progression increased significantly as ERCC1 (HR=12.00, 95% CI 1.08-133.35, p=0.04), GSTP1 (HR=6.01, 95% CI 1.09-33.01, p=0.004), XPD (HR=10.37, 95% CI 1.26-85.52, p=0.003), MGMT (HR=10.26, 95% CI 1.18-88.94, p=0.035) and BRCA1 (HR= 7.52, 95% CI 1.32-42.74, p=0.023) levels increased. Conclusions: Our results indicate that these biomarkers could be useful predictors of clinical response to platinum compounds in patients with advanced ovarian cancer who develop recurrent intra-abdominal disease. It is now planned to compare tailored and empiric therapy in a well-designed randomized trial. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2709.