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JOANNA SCHWARTZ, PHARM.D., BCOP, is Assistant Professor, Department of Pharmacy Practice, and Clinical Oncology Pharmacy Specialist, Albany College of Pharmacy and Health Sciences, Vermont Campus, 261 Mountain View Drive, Colchester, VT 05404 (joanna.schwartz{at}acphs.edu).

Purpose. To review the role of combination therapy in the treatment of metastatic breast cancer and to describe strategies to help manage adverse events associated with combination therapy. Summary. Although the median survival of patients with metastatic breast cancer has increased over the last several decades, new treatment options are needed to further improve survival and quality of life for these patients. Novel cytotoxic and noncytotoxic agents have recently been evaluated in combination regimens for patients with metastatic breast cancer. Combinations for metastatic breast cancer that appear in recently approved labeling include ixabepilone with capecitabine, and the targeted biological agent lapatinib in combination with capecitabine. Ixabepilone is the first of a new family of cytotoxic agents—the epothilones—to enter clinical practice. Similar to the taxanes, ixabepilone binds to and stabilizes intracellular microtubules, resulting in decreased DNA replication and cell proliferation. Ixabepilone possesses antitumor activity in taxane-resistant tumor cells and has been shown to significantly improve progression-free survival when used in combination with capecitabine in patients with taxane-resistant tumors. Lapatinib, an oral small-molecule inhibitor of human epidermal growth factor receptors-1 and -2, has been shown, when combined with capecitabine, to improve progression-free survival in patients with advanced metastatic breast cancer who had progressed on prior therapy. The combination of paclitaxel and bevacizumab carries approved labeling for treatment of metastatic breast cancer, although there are concerns about bevacizumab and the risk of toxicity. Conclusion. Ongoing clinical trials continue to define the role of novel antitumor agents in combination regimens for patients with metastatic breast cancer. Targeted agents are less likely to produce adverse events that are typical of cytotoxic chemotherapy but, because of their effects on specific molecular targets, may cause toxicities that were previously uncommon in cancer therapy. Index terms: Antineoplastic agents; Bevacizumab; Breast neoplasms; Capecitabine; Combined therapy; Ixabepilone; Lapatinib; Mechanism of action; Mortality; Neoplasm metastasis; Paclitaxel; Site of action; Toxicity