Initial chemotherapy choices for the treatment of newly diagnosed and metastatic breast cancer have dramatically changed over the past four decades, evolving from marginally effective non-anthracycline single agent therapies to non-anthracycline containing combinations, such as cyclo-phosphamide, methotrexate, and 5- fluorouracil (CMF) and CMF plus vincristine and prednisone (CMFVP). In the latter 1970s and throughout the 1980s, the use of anthracycline-containing regimens, such as 5-fluorouracil, adriamycin and cyclophosphomide, (FAC), cyclo-phosphamide, doxorubicin and 5-fluorouracil (CAF) and adriamycin and cyclophosphomide (AC), resulted in higher response rates and longer time-to-progression, but failed to show survival advantage in metastatic disease. During the 1980s many investigational agents were explored in clinical trials with hope of improvement in the patient’s response to therapy, duration of response and increased survival. Unfortunately, the majority of these agents failed to show benefit and/or produced unacceptable toxicities.
The taxanes are a class of anticancer agents that bind to and stabilize microtubules causing cell-cycle arrest and apoptosis (cell death). Paclitaxel, initially extracted from the bark of the Pacific yew, Taxus brevifolia, was identified in 1971 as part of a National Cancer Institute (NCI) program that screened medicinal plants for potential activity. Docetaxel was synthesized in 1986, using a precursor extracted from the needles of the European yew, T. baccata, and is similar to paclitaxel in its mechanism of action.
Results from clinical trials designed in the late 1980s have shown that taxanes are among the most active chemotherapy agents used in the management of metastatic breast cancer. Positive trials in the adjuvant and neoadjuvant setting have more recently changed practice standards. These agents may be considered the most powerful group of compounds developed in the 1990s.