title: 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.
abstract: OBJECTIVE
  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 Fcgamma 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.
  
  
  METHODS
  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 microg within 9 to 13 days.
  
  
  RESULTS
  The maximum tolerated dose was defined at 10, 20, 50, 200, and 200 microg 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 microg), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, Ludwig-Maximilans University, Munich Grosshadern, Germany. Alexander.Burges@med.uni-muenchen.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Burges
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Carolin
authors.initials: C
authors.lastname: Kümper
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbounova
authors.forename: Harald
authors.initials: H
authors.lastname: Sommer
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmalfeldt
authors.forename: Jacobus
authors.initials: J
authors.lastname: Pfisterer
authors.forename: Michail
authors.initials: M
authors.lastname: Lichinitser
authors.forename: Anatoliy
authors.initials: A
authors.lastname: Makhson
authors.forename: Vladimir
authors.initials: V
authors.lastname: Moiseyenko
authors.forename: Angelika
authors.initials: A
authors.lastname: Lahr
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schulze
authors.forename: Michael
authors.initials: M
authors.lastname: Jäger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ströhlein
authors.forename: Markus Maria
authors.initials: MM
authors.lastname: Heiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Gottwald
authors.forename: Horst
authors.initials: H
authors.lastname: Lindhofer
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000737:chemistry / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001201:Ascites / Q000628:therapy*; D017252:CD3 Complex / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000150:complications* / Q000276:immunology / Q000628:therapy*; D013997:Time Factors
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D017493:Leukocyte Common Antigens