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Effective Relief of Malignant Ascites in Patients with Advanced Ovarian Cancer by a Trifunctional Anti-EpCAM x Anti-CD3 Antibody: A Phase I/II Study

Authors' Affiliations: Departments of ¹ Obstetrics and Gynecology and ² Surgery, Ludwig-Maximilans University, Munich Großhadern, Germany; ³ Department for Obstetrics and Gynecology, University of Duisburg-Essen, Essen, Germany; ⁴ Research Center for Oncology and ⁵ Oncology Clinical Hospital, Moscow, Russia; ⁶ Department for Obstetrics and Gynecology, Ludwig-Maximilians University, Munich Maistrasse, Germany; ⁷ Department for Obstetrics and Gynecology, Technical University of Munich; ⁸ Fresenius Biotech GmbH, and ⁹ TRION Pharma GmbH, Munich, Germany; ¹⁰ Department for Obstetrics and Gynecology, University of Kiel, Kiel, Germany; ¹¹ Scientific Oncology Institute, St. Petersburg, Russia; and ¹² TRION Research GmbH, Martinsried, Germany

Requests for reprints: Alexander Burges, Marchioninistrasse 15 81377 Munich, Germany. Phone: 49-897-095-5843; Fax: 49-897-095-5844; E-mail: Alexander.Burges{at}med.uni-muenchen.de.

Purpose: Malignant ascites in ovarian carcinoma patients is associated with poor prognosis and reduced quality of life. The trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) enhances the antitumor activity by redirecting T cells and Fc receptor I/III–positive accessory cells to the tumor. This multicenter phase I/II dose-escalating study investigated tolerability and efficacy of i.p. catumaxomab application in ovarian cancer patients with malignant ascites containing epithelial cell adhesion molecule (EpCAM)–positive tumor cells.

Experimental Design: Twenty-three women with recurrent ascites due to pretreated refractory ovarian cancer were treated with four to five i.p. infusions of catumaxomab in doses of 5 to 200 µg within 9 to 13 days.

Results: The maximum tolerated dose was defined at 10, 20, 50, 200, and 200 µg for the first through fifth doses. Side effects included transient fever (83%), nausea (61%), and vomiting (57%), mostly CTCAE (Common Terminology Criteria for Adverse Events) grade 1 or 2. A total of 39 grade 3 and 2 grade 4 treatment-related adverse events (AE), 9 of them after the highest dose level (200 µg), were observed in 16 patients. Most AEs were reversible without sequelae. Treatment with catumaxomab resulted in significant and sustained reduction of ascites flow rate. A total of 22/23 patients did not require paracentesis between the last infusion and the end of study at day 37. Tumor cell monitoring revealed a reduction of EpCAM-positive malignant cells in ascites by up to 5 log.

Conclusion: I.p. immunotherapy with catumaxomab prevented the accumulation of ascites and efficiently eliminated tumor cells with an acceptable safety profile. This suggests that catumaxomab is a promising treatment option in ovarian cancer patients with malignant ascites.