Abstract 3516: Combinations of chemotherapy with bevacizumab in a xenograft model of human ovarian carcinoma

Ovarian cancer is the leading cause of death from gynecologic malignancy in women of the Western countries. The standard first-line therapy for this type of tumor is the combination of paclitaxel (PTX) and carboplatin. Vascular endothelial growth factor (VEGF) performs as an angiogenic and permeability factor in ovarian cancer, and its over-expression has been associated with poor prognosis. Inhibition of malignant ascites and tumor growth has been shown by blocking the VEGF/VEGFR pathway. Early clinical studies with bevacizumab, the monoclonal antibody directed against VEGF, have demonstrated efficacy in ovarian carcinoma patients as single and combined treatment. The aim of this study was to evaluate the effect of chemotherapy in combination with bevacizumab given at different regimens in an in vivo model of human ovarian carcinoma xenograft. Nude mice were transplanted intraperitoneally with 1A9-luc ovarian carcinoma cells, over-expressing luciferase, that allows to monitor the tumor growth and dissemination in the peritoneal cavity of the mice by bioluminescence imaging analysis. Mice were treated with PTX (20 mg/kg) or cisplatin (DDP, 3 mg/kg) as single therapy or in combination; bevacizumab (150 µg/mouse) was given concurrently for 3 weeks and either continued after the suspension of chemotherapy (maintenance regimen) or stopped. Untreated mice developed heavy tumor burden in the peritoneal cavity with a median survival time (MST) of approximately 24 days. PTX or DDP given alone only marginally affected the survival of the mice. The addition of bevacizumab to PTX or DDP significantly improved the survival of the mice with an increased life span (ILS) of 117% and 75% respectively; this was ameliorated by the continuation of bevacizumab treatment after chemotherapy (ILS = 158% and ILS = 100% respectively). The combined administration of PTX and DDP plus bevacizumab further improved the survival of the mice (ILS>190%); most importantly, maintaining the treatment with bevacizumab (up to 90 days) after the suspension of chemotherapy resulted in tumor free mice. Monitoring the tumor burden by bioluminescence imaging analysis confirmed the different tumor response among the treatment groups. These findings show a benefit from the combination of PTX/DDP plus bevacizumab in ovarian carcinoma, and are in favor of the maintenance regimen with bevacizumab. Supported by AIRC and Fondazione Cariplo Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3516. doi:10.1158/1538-7445.AM2011-3516