Strategies to decrease taxanes toxicities in the adjuvant treatment of early breast cancer

Taxanes are tubulin-targeting agents that are highly active in the treatment of breast cancer. The lack of cross-resistance and limited overlapping toxicities of taxanes with other agents, such as anthracycline, made it possible to incorporate them in the adjuvant treatment of early breast cancer. When used alone or in combination with other cytotoxic agents, taxanes significantly improved response rate, time to progression, disease-free and in some trials over-all survival in patients with advanced or metastatic breast cancer. Mature data are now emerging from the early randomized clinical trials that consistently demonstrate a clear survival benefit of taxanes when combined with anthracycline. However, increased toxicities, especially hematological toxicities, were also observed. Various strategies to decrease the taxanes toxicities have been explored, including appropriate dosing and scheduling to optimize the therapeutic index, sequential rather than concurrent use of anthracycline and taxanes, the use of growth factor support and the removal of anthracycline, with encouraging results. The development of novel taxanes with less toxicities and use of molecular markers to target patients with taxane-responsive tumors are in early clinical trials. This review focuses on safety issues of taxanes in the adjuvant treatment of early breast cancer. Strategies to reduce the taxane toxicity and future direction of taxane research in early breast cancer will be discussed.