The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial.
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.
Heiss
Markus M
MM
Department of Surgery, Cologne-Merheim Medical Center, University of Witten-Herdecke, Cologne, Germany.
Murawa
Pawel
P
Koralewski
Piotr
P
Kutarska
Elzbieta
E
Kolesnik
Olena O
OO
Ivanchenko
Vladimir V
VV
Dudnichenko
Alexander S
AS
Aleknaviciene
Birute
B
Razbadauskas
Arturas
A
Gore
Martin
M
Ganea-Motan
Elena
E
Ciuleanu
Tudor
T
Wimberger
Pauline
P
Schmittel
Alexander
A
Schmalfeldt
Barbara
B
Burges
Alexander
A
Bokemeyer
Carsten
C
Lindhofer
Horst
H
Lahr
Angelika
A
Parsons
Simon L
SL
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
D018033:Antibodies, Bispecific; C522419:catumaxomab
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