Catumaxomab in the Treatment of Malignant Ascites: The Evidence of its Therapeutic Value

Abstract

The trifunctional, bispecific antibody catumaxomab (anti-EpCAM x anti-CD3) is a new therapeutic strategy for epithelial cancer patients with symptomatic malignant ascites. The trifunctionality has the advantage of binding tumor cells and simultaneously two different immune effector cells (e.g. macrophages and T-lymphocytes). The unique binding specifities of catumaxomab induce an effective destruction of tumor cells, including those resistant to apoptosis, through different mechanisms, i.e. perforin-mediated lysis, antibody-mediated phagocytosis, and cytokine release. Moreover, a possible long-lasting humoral and cellular antitumor response was shown in a mouse model with a surrogate bispecific trifunctional antibody binding to mouse CD3. Catumaxomab (Removab®) is the first medication approved by the EMEA (European Medicines Agency) for the treatment of malignant ascites due to EpCAM-positive carcinomas where no standard therapy is available or no longer feasible. The safety profile is acceptable. Adverse events associated with catumaxomab are manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab is a promising new therapy for malignant acites even in heavily pretreated patients. Intraperitoneal treatment with catumaxomab plus paracentesis demonstrated clinically relevant benefit in patients with recurrent malignant ascites. Significantly prolonged puncture-free survival (46 vs. 11 days) as well as prolonged time to first need of therapeutic puncture (77 vs. 13 days) was shown in comparison to paracentesis alone ( P < 0.0001).