Volume 5, Number 4, Supplement 3 (April 2008)

Original Contributions

2

Modulating drug resistance in metastatic breast cancer

Edith A. Perez, MD

Mayo Clinic, Jacksonville, FL

Taxanes are widely used for the treatment of metastatic breast cancer (MBC). Many patients, however, exhibit intrinsic drug resistance or develop it following exposure to commonly used chemotherapeutics. Consequently, their treatment options are limited, and the prognosis is often poor. Resistance can develop to a single drug or to several structurally and functionally distinct agents, a phenomenon known as multidrug resistance (MDR). Drug resistance in general, and the MDR phenotype in particular, represent major challenges to treatment of advanced disease, since they are frequently the cause of disease progression in patients with breast cancer. This article addresses the key mechanisms underlying resistance to chemotherapy in breast cancer, which provides a basis for development of novel compounds that can treat drug-resistant disease. Novel agents such as nab-paclitaxel, ixabepilone, and modulators of apoptosis are discussed that are proving to be effective in the treatment of drug-resistant MBC.

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10

Taxane alternatives: efficacy and toxicity

Hope S. Rugo, MD

University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA

Taxane therapy is widely used for the treatment of metastatic breast cancer (MBC). Many patients, however, do not respond or subsequently relapse due to drug resistance. The use of standard paclitaxel and docetaxel is further limited by the solvents required for parenteral administration of these hydrophobic agents, such as polyethylated castor oil, that can significantly limit dose escalation, increase toxicity, complicate administration of chemotherapy, and alter drug pharmacokinetics. Nanoparticle albumin-bound (nab) paclitaxel is a novel, water-soluble formulation of paclitaxel conjugated to albumin that obviates the need for such toxic solvents. Uptake of this conjugate is facilitated by albumin-mediated transcytosis across endothelial cells into the tumor, thus increasing the effective tumor paclitaxel concentration and reducing systemic toxicity. Clinical trials have demonstrated that nab-paclitaxel is effective for the treatment of MBC, both as monotherapy and in combination regimens. Compared with standard paclitaxel, treatment with nab-paclitaxel is associated with a lower incidence of adverse events, particularly hypersensitivity reactions.

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Funding for this supplement was provided by Abraxis Oncology

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