A preliminary study on treatment of human breast cancer xenografts with a cocktail of paclitaxel, doxorubicin, and 131I-anti-epithelial cell adhesion molecule (9C4)

Naiim S. Ali; John M. Akudugu; Roger W. Howell

doi:10.4103/wjnm.WJNM_9_18

World Journal of Nuclear Medicine, Table of Contents

CC BY-NC-ND 4.0 · World J Nucl Med 2019; 18(01): 18-24
DOI: 10.4103/wjnm.WJNM_9_18

Original article

A preliminary study on treatment of human breast cancer xenografts with a cocktail of paclitaxel, doxorubicin, and ¹³¹I-anti-epithelial cell adhesion molecule (9C4)

Naiim S. Ali

¹Division of Radiation Research, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA

²Department of Radiology, University of Vermont Medical Center, Burlington, VT 05401, USA

,

John M. Akudugu

¹Division of Radiation Research, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA

³Department of Medical Imaging and Clinical Oncology, Division of Radiobiology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg 7505, South Africa

,

Roger W. Howell

¹Division of Radiation Research, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA

› Author Affiliations

Abstract

Triple-negative breast cancer often has devastating outcomes and treatment options remain limited. Therefore, different treatment combinations are worthy of testing. The efficacy of a cocktail of paclitaxel, doxorubicin, and ¹³¹I-anti-epithelial cell adhesion molecule (EpCAM) (9C4) to treat breast cancer was tested. Efficacy was tested with an MDA-MB-231 human breast cancer xenograft model. Anti-EpCAM (9C4) was demonstrated to bind to MDA-MB-231 human adenocarcinoma cells in vitro. Subsequently, mice-bearing MDA-MB-231× enografts were treated with either ¹³¹I-anti-EpCAM (9C4), unlabeled anti-EpCAM (9C4), paclitaxel, doxorubicin, or a cocktail of all of the agents. Tumor volume was measured for up to 70-day postinjection. Exponential regression was performed on tumor growth curves for each of the therapy groups. Statistical comparison of the growth constants λ of the regression models for each of the treatment groups with that of the cold antibody and control groups was done using extra sum-of-square F-tests. Biexponential clearance of ¹³¹I-anti-EpCAM (9C4) was observed with biological clearance half-times of 1.14 and 17.6 days for the first and second components, respectively. The mean growth rate of the tumors in animals treated with a cocktail of all of the agents was slower than in those treated with unlabeled anti-EpCAM (9C4) (P = 0.022). These preliminary data suggest that a cocktail of ¹³¹I-anti-EpCAM (9C4), paclitaxel, and doxorubicin may be suitable for treating breast cancers with high expression of EpCAM.

Keywords

Chemotherapy - doxorubicin - epithelial cell adhesion molecule - iodine-131 - monoclonal antibody - paclitaxel - radioimmunotherapy

Full Text

References

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