Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer.
The taxanes docetaxel (Taxotere; Sanofi-Aventis U.S. LLC, Bridgewater, NJ) and paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) are highly active agents in metastatic breast cancer and may represent a safer alternative to anthracycline-based regimens when combined with the human epidermal growth factor receptor (HER)-2-targeted agent trastuzumab (Herceptin(R); Genentech Inc., South San Francisco, CA). A number of preclinical and early clinical studies have evaluated the feasibility, duration, and appropriate dosing schedule(s) for taxane-trastuzumab combinations in HER-2-positive metastatic breast cancer. Preclinical studies of the taxanes in combination with trastuzumab demonstrate synergistic interactions of trastuzumab with docetaxel and additive interactions with paclitaxel. Even though not supported by head-to-head studies, clinical trial results indicate the response rates with docetaxel-trastuzumab combinations may be higher than those with paclitaxel-trastuzumab, although there is a lack of clear crosstrial differences in other clinical benefits. Weekly taxane-trastuzumab regimens have been shown to offer superior disease control. Results from two large, phase III trials that examined the addition of carboplatin to a taxane-trastuzumab doublet did not demonstrate a difference in survival with carboplatin. In one study, the addition of carboplatin to paclitaxel-trastuzumab therapy resulted in a higher response rate and longer progression-free survival time; in the second study, the docetaxel-trastuzumab and docetaxel-trastuzumab-carboplatin combinations were equally effective. Ongoing correlative studies of taxanes, as well as newer formulations such as nanoparticle albumin-bound paclitaxel, in combination with trastuzumab will inform clinical practice regarding the optimal agent, schedule, and use of these highly effective regimens.
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