Comparison of paclitaxel and docetaxel as single agents or in combination with bevacizumab in the 4T1 metastatic breast tumor line

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Paclitaxel (Taxol) and docetaxel (Taxotere) are anticancer agents in a class of compounds called taxanes which act by stabilizing microtubules and inducing apoptosis. Bevacizumab (Avastin) is a humanized monoclonal antibody which disrupts tumor vascularization by blocking signaling through the vascular endothelial growth factor (VEGF) receptor. Some benefit has been reported by combining bevacizumab with standard chemotherapies in preclinical and clinical studies. In addition, experiments comparing single agent activity of paclitaxel to docetaxel have produced conflicting results. To examine potential additive activity of bevacizumab with taxanes and to further compare efficacy of these compounds, we examined single agent and combination antitumor activity in the 4T1 orthotopic metastatic breast cancer model in immunocompetent mice. Paclitaxel was dosed at 15 mg/kg once daily for five treatments (QDx5) while docetaxel was administered every other day for three treatments at 12.5 mg/kg (QODx3); bevacizumab was dosed at 10 mg/kg every three days for five treatments (Q3Dx5). Significant endpoints included tumor growth inhibition (TGI), metastasis, tumor regression, and weight loss. Tested alone, paclitaxel produced only moderate TGI in this model (21%), which was not increased by bevacizumab co-treatment. However, single agent docetaxel treatment resulted in significant tumor growth inhibition (p<0.001), which was potentiated by co-administration of bevacizumab; decreased metastasis was reported with docetaxel versus paclitaxel treatment. Weight loss in single agent and combination groups was comparable. Taken together, these results demonstrate increased activity of docetaxel compared with paclitaxel in this model of metastatic breast cancer. Additional combination testing with docetaxel and bevacizumab in relevant tumor models is warranted.