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| |  Efficacy and Safety of Trifunctional Antibody, Catumaxomab, Documented in Phase 2/3 Study: Presented at ASCO By Cameron Johnston CHICAGO, IL -- June 4, 2007 -- Intraperitoneal injections of the trifunctional antibody catumaxomab in patients with malignant ascites resulting from primary abdominal tumours have shown a clear advantage over the standard treatment for this condition. Phase 2/3 data were presented here at the 43rd American Society of Clinical Oncology Annual Meeting (ASCO) by Simon Parsons, MD, department of surgery, Nottingham University Hospital, Nottingham, United Kingdom. According to Dr. Parsons, malignant ascites are a common result of advanced abdominal cancers, particularly ovarian cancer. There can be 1 of 2 causes: the lymphatic system becomes blocked and is not able to drain fluids from the abdominal cavity; or the vascular endothelial growth factor that triggers the growth of cancer cells causes the blood vessel walls to leak fluid into the abdominal cavity. Traditionally, the only way to treat this build-up was through paracentesis -- the peritoneal cavity is punctured and drained of the fluids. In their study, Dr. Parson and colleagues in Germany, Britain, and Poland enrolled 129 patients with symptomatic malignant ascites, who either no longer responded to, or could no longer be treated with chemotherapy. Half of the patients had ovarian cancer; the rest had other forms of epithelial tumours (gastric 51%, breast 10%, pancreas 7%, intestines 6%, and miscellaneous 26%). The researchers randomised 85 patients to catumaxomab plus paracentesis and 44 patients to paracentesis alone. Three quarters of patients in each group had at least 2 paracentesis procedures. Catumaxomab was administered intraperitoneally at doses of 10, 20, 50, and 150 mcg through 6-hour infusions, following paracentesis on days 0, 3, 7, and 10. The primary endpoint of the study was the puncture-free survival time (i.e., the time up to the first therapeutic paracentesis) or death. Secondary endpoints were puncture-free time, relief of ascites symptoms, and safety and tolerability of catumaxomab. Catumaxomab-treated patients achieved a median puncture-free survival of 52 days, compared with 11 days in the control group (P <.0001). Thus, the primary endpoint of the study was achieved. For the secondary endpoint, puncture free-time, catumaxomab patients had a median improvement of 71 days compared with 11 days in the control group (P <.0001). Patients who received catumaxomab were significantly more likely not to have symptoms of abdominal pain, nausea, early satiety, abdominal swelling, and anorexia compared with patients in the control group. On average, around 60% of patients receiving catumazomab were completely free, or largely free of those symptoms. By comparison, in the control group, 20% to 30% of patients were free of those symptoms. In terms of biological markers, patients in the catumaxomab group also showed a significant reduction in the number of tumour cells in the ascites fluid. This was accompanied by an increase in the number of CD45 positive leucocytes, a higher interleukin-2 and interferon gamma secretion, as well as an increased expression of the activation marker CD69 on T-cells, which indicates a possible immunological effect on the tumour cells of the trifunctional antibody. Catumaxomab displayed a very good safety profile. None of the deaths that occurred during the study could be attributed to catumaxomab and approximately 80% of patients were able to receive all 4 treatments with the drug as planned. The study has now been expanded to include a total of 258 patients and the results of the expanded trial have been much the same as what was seen in the preliminary groups. One exception in the expanded study is that patients who had gastric cancer appear to fare even better than those with ovarian cancer. Catumaxomab is a novel trifunctional antibody that acts on 2 different antigen binding sites, the EpCAM (Epithelial Cell Adhesion Molecule) and the T-cell sites. It also combines the characteristics of classical monoclonal antibodies. When approved for more widespread use, catumaxomab could significantly improve the treatment of patients within this high morbidity group, who currently have no effective therapy option. This study was funded by Fresenius Biotech GmbH, which developed catumaxomab in cooperation with Trion Pharma, both of Munich, Germany.
[Presentation title: Treatment of Ovarian Cancer Patients With Malignant Ascites Using the Trifunctional Antibody Catumaxomab: Results of a Phase II/III Study. Poster 5520]
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