title: The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial.
abstract: Malignant ascites is a common manifestation of advanced cancers, and treatment options are limited. The trifunctional antibody catumaxomab (anti-epithelial cell-adhesion molecule x anti-CD3) represents a targeted immunotherapy for the intraperitoneal (i.p.) treatment of malignant ascites secondary to epithelial cancers. In this phase II/III trial (EudraCT 2004-000723-15; NCT00836654), cancer patients (n = 258) with recurrent symptomatic malignant ascites resistant to conventional chemotherapy were randomized to paracentesis plus catumaxomab (catumaxomab) or paracentesis alone (control) and stratified by cancer type (129 ovarian and 129 nonovarian). Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 mug, respectively. The primary efficacy endpoint was puncture-free survival. Secondary efficacy parameters included time to next paracentesis, ascites signs and symptoms and overall survival (OS). Puncture-free survival was significantly longer in the catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition, catumaxomab patients had fewer signs and symptoms of ascites than control patients. OS showed a positive trend for the catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab showed a clear clinical benefit in patients with malignant ascites secondary to epithelial cancers, especially gastric cancer, with an acceptable safety profile.
authors.affiliation: Department of Surgery, Cologne-Merheim Medical Center, University of Witten-Herdecke, Cologne, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heiss
authors.forename: Pawel
authors.initials: P
authors.lastname: Murawa
authors.forename: Piotr
authors.initials: P
authors.lastname: Koralewski
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kutarska
authors.forename: Olena O
authors.initials: OO
authors.lastname: Kolesnik
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Ivanchenko
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Dudnichenko
authors.forename: Birute
authors.initials: B
authors.lastname: Aleknaviciene
authors.forename: Arturas
authors.initials: A
authors.lastname: Razbadauskas
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.forename: Elena
authors.initials: E
authors.lastname: Ganea-Motan
authors.forename: Tudor
authors.initials: T
authors.lastname: Ciuleanu
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmittel
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmalfeldt
authors.forename: Alexander
authors.initials: A
authors.lastname: Burges
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Horst
authors.initials: H
authors.lastname: Lindhofer
authors.forename: Angelika
authors.initials: A
authors.lastname: Lahr
authors.forename: Simon L
authors.initials: SL
authors.lastname: Parsons
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D001201:Ascites / Q000150:complications* / Q000188:drug therapy*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000150:complications* / Q000188:drug therapy*; D019152:Paracentesis
chemical_list: D018033:Antibodies, Bispecific; C522419:catumaxomab
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