Options for the Treatment of Patients with Taxane-Refractory Metastatic Breast Cancer

The application of taxane chemotherapy to the treatment of early-stage and advanced breast cancer has resulted in significant improvements in disease-free and overall survival. As a consequence of these improvements in disease outcome, oncologists must face the new challenge of developing additional therapies that are effective against taxane-resistant disease and are associated with a favorable toxicity profile. This article discusses some of the chemotherapeutic options available for the treatment of patients with taxane-resistant metastatic breast cancer. Newer formulations of traditional microtubule-stabilizing agents, such as albumin- bound paclitaxel, which uses a more favorable vehicle for administration compared with conventional paclitaxel, have demonstrated efficacy in this setting. Several novel microtubule-targeting agents have been shown to be less susceptible to traditional mechanisms of taxane resistance, such as the multidrug resistance phenotype associated with increased activity of the P-glycoprotein drug efflux system and the development of structural changes in tubulin. Examples of these therapies include the vinca alkaloids, such as vinorelbine and vinflunine; epothilones; and eribulin. Traditional antimetabolites, such as gemcitabine and capecitabine, used as monotherapy or combination chemotherapy have also shown efficacy in the treatment of patients with taxane-resistant breast cancer. A greater understanding of the mechanism of drug resistance, as it pertains to taxanes, will enable further development and the effective application of chemotherapeutic agents that will circumvent drug resistance and result in improvement in breast cancer control.