Future directions of paclitaxel-based therapy of breast cancer.

In the past 15 years, substantial progress has been made in the treatment of breast cancer, but management of women with breast cancer is still not curative in many patients. One important goal of new treatment strategies is that of defining criteria to specifically indicate therapies so that therapeutic benefit will no longer result from the indiscriminate application of treatment to all patients within a broad category of risk. This approach could be applied to paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). The taxane is one of the most active new drugs developed for women with breast cancer. A number of conventional comparative trials are ongoing to assess its role in different stages of the disease. Some of its features, however, are suitable to explore more specific and relevant questions. Possibly because of paclitaxel's documented antiangiogenic properties, its high efficacy in combination could also provide an as yet unproven survival advantage in advanced breast cancer, with the drug being administered for adequately prolonged periods of time as a single agent after initial induction of response. In addition, available evidence suggests that patients with poor prognosis associated with overexpression of c-erb B2 (HER2) have a higher probability of responding to paclitaxel than patients with HER2-negative tumors. The clarification of this possibility is a priority. Should HER2 status be a predictor of response to paclitaxel and paclitaxel-based therapy, the use of the drug could be tailored to specific patient characteristics. The ability to discriminate between paclitaxel as a therapeutic option or a therapeutic indication is one of the challenges of the future development of this important drug.