Purpose: Malignant ascites in ovarian carcinoma patients is associated with poor prognosis and reduced quality of life. The trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3) enhances the antitumor activity by redirecting T cells and Fcγ 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 μg within 9 to 13 days. Results: The maximum tolerated dose was defined at 10, 20, 50, 200, and 200 μg 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 μg), 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.

PURPOSE The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) -positive locally recurrent/metastatic breast cancer (LR/MBC). PATIENTS AND METHODS Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior adjuvant trastuzumab, prior (neo)adjuvant taxane, hormone receptor status, and measurable disease and were randomly assigned to receive docetaxel 100 mg/m(2) plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. The primary end point was progression-free survival (PFS). Additional end points included overall survival, response rate (RR), safety, quality of life, and translational research. Results Baseline characteristics of the 424 patients were balanced between treatment arms. Most patients had visceral metastases, 43% had a disease-free interval less than 12 months, and 85% had measurable disease. Median follow-up was 26 months. The hazard ratio for investigator-assessed PFS was 0.82 (95% CI, 0.65 to 1.02; P = .0775; median PFS, 13.7 v 16.5 months in the non-bevacizumab and bevacizumab arms, respectively; PFS events in 72%). The Independent Review Committee-assessed PFS hazard ratio was 0.72 (95% CI, 0.54 to 0.94; P = .0162; median PFS, 13.9 v 16.8 months, respectively; PFS events in 53%). The RR was 70% versus 74%, respectively (P = .3492). Grade ≥ 3 febrile neutropenia and hypertension were more common with bevacizumab-containing therapy. High baseline plasma vascular endothelial growth factor A (VEGF-A) concentrations were associated with greater bevacizumab benefit (not statistically significant). CONCLUSION Combining bevacizumab with docetaxel and trastuzumab did not significantly improve investigator-assessed PFS. The potential predictive value of plasma VEGF-A is consistent with findings in HER2-negative LR/MBC, warranting prospective evaluation.

The objective of this study is to assess the effect of oral ibandronate on bone pain and quality of life in women with metastatic bone disease from breast cancer. In two double-blind, placebo-controlled studies, 564 patients were randomised to receive oral ibandronate, 50mg once daily, or placebo for up to 96 weeks. Throughout the studies, we assessed bone pain (on a 5-point scale from 0=none to 4=intolerable), analgesic use (7-point scale) and quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 [EORTC QLQ-C30], 100-point scale). Oral ibandronate significantly reduced and maintained bone-pain scores below baseline throughout the 96-week study period (at endpoint, -0.1 vs +0.2, P=0.001 vs placebo). Analgesic use increased in both groups; however, the increase was significantly less in the ibandronate group (0.60 vs 0.85, P=0.019). Although quality of life deteriorated during the study, the decrease in quality of life was significantly lower with ibandronate therapy (-8.3 vs -26.8, P=0.032). Drug-related adverse events were generally minor and as expected with oral bisphosphonates. Oral ibandronate had beneficial effects on bone pain and quality of life and was well tolerated. These results suggest that this treatment is of considerable clinical value as a co-analgesic to patients with painful bone metastases.

These results indicate that 6 mg i.v. ibandronate is effective and safe in the treatment of bone metastases from breast cancer.

Monthly injections of ibandronate 2 mg IV neither reduced bone morbidity nor prolonged survival in the overall population of stage II/III multiple myeloma patients.