open access: Commentary: VEGF Trap for the treatment of malignant ascites : The Lancet Oncology

"About 10% of all cases of ascites are caused by a malignant disease. In developed countries the most common neoplasm associated with ascites is ovarian cancer. The pathophysiology of malignant ascites is multifactorial, and its molecular pathogenesis is only poorly understood. Ascites formation can result from obstruction of lymph vessels by tumour cells, resulting in incomplete absorption of intraperitoneal fluid and protein,1 especially in patients with lymphoma or breast cancer. Since malignant ascites is usually an exsudate with a high protein concentration, an increased vascular permeability has been implicated in its pathogenesis.2 In addition to mechanical obstruction and cytokines, the pathophysiology of malignant ascites includes hormonal mechanisms. Because of the accumulation of ascites caused by obstructed lymph vessels, the circulating blood volume is reduced, which results in activation of the renin-angiotensin-aldosterone system that is followed by sodium retention.

Unlike the established therapeutic options for the underlying malignancy, there is no generally accepted gold standard for the management of malignant ascites...."

"...With respect to the clinical implications of the results (Walter Gotlieb and colleagues7 in The Lancet Oncology), symptom relief has to be weighed against discomfort and potentially life-threatening adverse events (three patients had fatal gastrointestinal complications in the aflibercept group vs one in the placebo group), since the treatment is applied to patients in a highly palliative situation. Careful patient selection could reduce the incidence of gastrointestinal perforations. However, before a general recommendation of aflibercept for the treatment of malignant ascites can be made, further studies, including comparative effectiveness research,8 are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice."