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
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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. / Burges, Alexander; Wimberger, Pauline; Kümper, Carolin; Gorbounova, Vera; Sommer, Harald; Schmalfeldt, Barbara; Pfisterer, Jacobus; Lichinitser, Michail; Makhson, Anatoliy; Moiseyenko, Vladimir; Lahr, Angelika; Schulze, Elisabeth; Jäger, Michael; Ströhlein, Michael A; Heiss, Markus Maria; Gottwald, Thomas; Lindhofer, Horst; Kimmig, Rainer.
In: CLIN CANCER RES, Vol. 13, No. 13, 01.07.2007, p. 3899-905.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -