Novel anti-tubulin cytotoxic agents for breast cancer

Abstract

Regardless of stage of disease, cytotoxic chemotherapy remains an important part of the treatment paradigm for breast cancer. Anthracyclines and taxanes are the most active agents; however, limitations with their use exist. These include a maximum lifetime dose and tumor resistance with anthracycline, hypersensitivity reactions and cumulative toxicity with taxanes. Therefore, to meet these challenges, the development of new cytotoxics and novel taxane formulations is an important area of active research. Several recent advances have been made. Epothilones represent a novel group of cytotoxic agents, with proven activity in breast cancer. Nanoparticle drug delivery systems have led to the development of ABI-007, which has demonstrated superior response rates than 3-weekly paclitaxel, with a lower risk of hypersensitivity reactions. To circumvent the problem of taxane resistance, larotaxel, a semisynthetic taxoid, and vinflunine, a synthetic vinca alkaloid, have been developed with encouraging clinical results to date. Eribulin, a synthetic derivative of halichondrin has recently entered Phase III trials based on encouraging activity in heavily pretreated patients. A further novel approach is the conjugation of cytotoxic agents to targeted agents, such as with trastuzumab–MCC-DM1. Elucidating the relative importance of these agents and incorporating them into existing treatment paradigms is a significant challenge for the future.