Intraperitoneal VEGF Inhibition Using Bevacizumab: A Potential Approach for the Symptomatic Treatment of Malignant Ascites?

Abstract

Despite overall improvements in oncological care in the palliative setting, symptomatic malignant ascites remains a severe clinical problem. This form of effusion is known to be widely resistant to established modes of systemic therapy. Accordingly, frequent paracentesis often represents the only effective way for symptom relief in patients with advanced cancer. This invasive mode of therapy, however, is often very burdensome for the patient who is already severely distressed by the underlying malignancy. Recently, the trifunctional monoclonal antibody catumaxomab given i.p. has shown symptom relief in patients with ovarian cancer and malignant ascites. On another front, the release of vascular endothelial growth fac-

Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study – AIO SUP-0108

“…agents are readily absorbed by the peritoneal tumour tissue. Thirdly, this route was likewise successfully used in most pre-clinical animal models [7,14] The overall median ParFS, based on observed events in all patients, was 13 d for the whole study population (95% CI: 10e15 d). This is in accordance with the assumed median of 14 d, which formed the basis for the statistical design calculation of the trial.…”

“…), in patients with ascites secondary to a variety of solid tumours, predominantly ovarian cancer. However, the sample sizes were rather small, ranging from 1e9 patients [7,12]. For the largest series, published in abstract form, ElShami et al reported resolution or at least distinctly delayed reaccumulation of ascites in all of the nine patients enrolled, after only one i.p.…”

“…Bevacizumab was chosen as it is known that VEGF plays a decisive role e not only in angiogenesis but also in the pathophysiology of malignant ascites, by augmenting the permeability of microvasculature and of the peritoneal membrane [7,10,11]. In animal models, the expression level in cancer cells was markedly associated with the production of ascites, while VEGF injections increased the permeability of pre-existing small vessels lining the peritoneum.…”

“…In animal models, the expression level in cancer cells was markedly associated with the production of ascites, while VEGF injections increased the permeability of pre-existing small vessels lining the peritoneum. Following promising data on peritoneal influx blocking and impressive ascites remissions in in vivo models [7], a number of clinical case series provided beneficial results for bevacizumab, especially when given intraperitoneal (i.p. ), in patients with ascites secondary to a variety of solid tumours, predominantly ovarian cancer.…”

“…Recently translational research as well as clinical results from small case series have suggested a potential role of the vascular endothelial growth factor (VEGF) in the development process of malignant ascites [1,7].…”