Abstract 4404: Microparticle generation and activation after treatment with paclitaxel and bavituximab combination therapy in metastatic breast cancer
Authors: Marilyn T. Marron, Pavani Chalasani, Daniel Camacho, Maria Iannone, Kathy Schmidt, Alison Stopeck
Journal: Cancer Research (2012)

Abstract Background: Breast cancer is the leading cause of life-threatening malignancy affecting women and the second leading cause of female cancer death in the United States. Weekly paclitaxel, alone or in combination with other chemotherapies, has proven to be an effective and well-tolerated therapy for patients with metastatic disease. Due to the tumor's dependence on vascularization for progression, survival and dissemination, targeting a tumor's vascular network is an important additional cancer management strategy. Bavituximab, a monoclonal antibody developed by Peregrine Pharmaceuticals against phosphatidylserine (PS), is a vascular disrupting agent designed to selectively attack tumor blood vessels already in existence. Under normal conditions, PS is localized to the internal surface of the plasma membrane. However, PS is preferentially localized on the outer surface of vascular endothelial cells in tumors, possibly due to stress conditions in the tumor microenvironment. Bavituximab is able to localize and bind specifically to PS in tumor vessels in a α2-glycoprotein 1 dependent manner, mediating the binding of host effector cells to the tumor vascular endothelium. This leads to vessel damage, vascularity reduction, necrosis, and growth retardation within the tumor. Microparticles are vesicles that are released from cells after activation, stress, death, or malignant transformation. Elevated levels of microparticles derived from platelets, endothelial cells, and/or leukocytes have been associated with several disease states, including cancer, however, the effect of anti-angiogenic or vascular disrupting agents on microparticle production is unclear. We investigated microparticle formation in our patients at baseline, in response to Paclitaxel chemotherapy, and after addition of Bavituximab. Patients and Methods: We initiated a phase I clinical trial in patients with Her-2 negative metastatic breast cancer treated with paclitaxel (80 mg/m2)on a weekly schedule for 3 out of 4 weeks, and weekly bavituximab (3 mg/kg) for 4 out of 4 weeks. Each cycle was defined as 4 weeks of therapy. Microparticles were isolated from peripheral blood and examined by flow cytometric phenotyping. Leukocyte, endothelial cell, and activated platelet microparticles were quantified and longitudinal trends analyzed. Five patients have been enrolled to date with additional patients accruing. At presentation, the longitudinal trends in microparticle formation from platelets, endothelial cells, and leukocytes will be presented in response to weekly Paclitaxel versus combined Paclitaxel and Bavituximab therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4404. doi:1538-7445.AM2012-4404