Taxanes: The Role in Metastatic Breast Cancer and Beyond

Abstract

In the 1990s, the taxanes emerged as the most important new class of cytotoxics for the treatment of breast cancer. Following a classical drug development paradigm, paclitaxel and docetaxel were first studied in metastatic breast cancer. Once their efficacy in the metastatic setting was established, research into other areas rapidly proceeded. Indeed, much research has ensued with the taxanes in both the adjuvant and neoadjuvant settings. Moreover, as we enter a new era of genomics and molecularly targeted therapies, the need to evaluate the taxanes within new frameworks becomes clear. To that end, the cooperative groups are evaluating novel combination therapies, such as docetaxel, cisplatin, and trastuzumab (TCH), as well as incorporating molecular markers, such as p53 mutations, into the statistical design to test hypotheses that certain groups of patients may respond differently to therapy than others. The following supplement developed from the Proceedings of a Satellite Symposium held on March 19, 2002 prior to 3rd European Breast Cancer Conference (EBCC-3) meeting in Barcelona, Spain. The focus of the presentations was docetaxel and docetaxelbased regimens in breast cancer. Dr Jean-Marc Nabholtz reviews the rationale for and results of docetaxel/anthracycline combinations in metastatic disease. Drs John Crown and Marc Pegram describe the development and rationale for platinum/ taxane/trastuzumab combinations, both in the metastatic and adjuvant setting. Results from early studies are reviewed. Dr. Andrew Hutcheon reviews the NSABP trials and the studies recently completed at the University of Aberdeen, Scotland, of docetaxel in the neoadjuvant setting. Positive findings with respect to improved pCR rates were noted when docetaxel was incorporated into the neoadjuvant chemotherapy regimen. Finally, the extensive clinical development of the taxanes for early stage breast cancer is examined. Numerous clinical trials have been undertaken to evaluate taxanes in the adjuvant setting, and results from the first generation of trials are emerging. These data are reviewed and placed into context with respect to ongoing trials, which seek to define the optimal sequence and schedule for adjuvant taxanes. Taken together, there is a wealth of encouraging, positive data regarding docetaxel in the treatment of breast cancer. As the new century begins, it is our challenge to critically examine these research findings and to continue to develop new trials to answer the questions that emerging data inevitably raise in order to best determine the future of breast cancer treatment.