Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

Abstract

Abstract. Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment.

Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab

“…Nevertheless, it is conceivable that these different amounts of serum sEpCAM might pass through the peritoneal barrier and accumulate in the peritoneal cavity to even higher concentrations in patients with malignant ascites driven by the high oncotic pressure. Similar concentrations as for sEpCAM were described for the soluble VEGF protein in ascites [ 26 ] but, in contrast to the observations made with catumaxomab, binding of VEGF by bevacizumab seems to positively impact the course of the disesase [ 27 ].…”

Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data

“…Given the fact that the effects of bevacizumab monotherapy were not found to be significantly dependent on whether the drug is intravenously or intraperitoneally administered [ 59 ], we proceed with the reproduction of the results of a series of in vivo experiments in mice intraperitoneally treated with bevacizumab. In particular, eight in vivo experiments conducted in mice bearing breast (KPL-4 cell line), lung (H226 cell line), head and neck (SCC1 cell line) as well as colon (HCT116, HT29, HCP40 and HP40 cell lines) tumour xenografts have been selected from relevant literature [ 60 – 62 ] in order to fit the model to actual experimental data.…”

Endostatin improves cancer-associated systemic syndrome in a lung cancer model

“…A previous study reported that the level of circulating VEGF correlates with the severity of CASS in tumor-bearing mice and human cancer patients, and that anti-VEGF agents could improve organ function (8). As a consequence of the off-tumor target effects, improvements to organ function and alterations in chemotoxic tolerance may be the most important mechanisms with a survival benefit in cancer patients with CASS (8,24).…”