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World J Nucl Med. 2019 Jan-Mar;18(1):18-24. doi: 10.4103/wjnm.WJNM_9_18.

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

Author information

1
Division of Radiation Research, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
2
Department of Radiology, University of Vermont Medical Center, Burlington, VT 05401, USA.
3
Department of Medical Imaging and Clinical Oncology, Division of Radiobiology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg 7505, South Africa.

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

Conflict of interest statement

John M. Akudugu and Roger W. Howell hold United States patents on related technology (US Patent No. 8,874,380, US Patent No. 9,623,262, and US Patent No. 9,804,167 B2.

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