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

TY - JOUR

T1 - 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

AU - Burges, Alexander

AU - Wimberger, Pauline

AU - Kümper, Carolin

AU - Gorbounova, Vera

AU - Sommer, Harald

AU - Schmalfeldt, Barbara

AU - Pfisterer, Jacobus

AU - Lichinitser, Michail

AU - Makhson, Anatoliy

AU - Moiseyenko, Vladimir

AU - Lahr, Angelika

AU - Schulze, Elisabeth

AU - Jäger, Michael

AU - Ströhlein, Michael A

AU - Heiss, Markus Maria

AU - Gottwald, Thomas

AU - Lindhofer, Horst

AU - Kimmig, Rainer

PY - 2007/7/1

Y1 - 2007/7/1

N2 - 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 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.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 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.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.

AB - 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 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.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 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.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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies

KW - Antigens, CD3

KW - Antigens, CD45

KW - Antigens, Neoplasm

KW - Ascites

KW - Cell Adhesion Molecules

KW - Female

KW - Humans

KW - Immunotherapy

KW - Maximum Tolerated Dose

KW - Middle Aged

KW - Ovarian Neoplasms

KW - Time Factors

U2 - 10.1158/1078-0432.CCR-06-2769

DO - 10.1158/1078-0432.CCR-06-2769

M3 - SCORING: Journal article

C2 - 17606723

VL - 13

SP - 3899

EP - 3905

JO - CLIN CANCER RES

JF - CLIN CANCER RES

SN - 1078-0432

IS - 13

ER -