The management of human epidermal receptor-2 (HER-2) negative metastatic
breast cancer (MBC) is usually problematic, since no standard
therapy exists in this setting. For some patients,
combination chemotherapy represents a valuable approach, although its use is often limited by the risks of increased toxicity as well as impairments in quality of life (QoL) that often outweigh the marginal efficacy benefit. Against this background, the use of
taxanes, either
paclitaxel or
docetaxel, in combination with
gemcitabine as first-line treatment of HER-2 negative MBC is supported by the evidence of the single-agent activity of these drugs, beneficial pharmacological interactions, different mechanisms of action and largely non superimposable toxicity profiles. A number of phase II studies have explored the activity of a
taxane plus
gemcitabine in both chemonaïve and pretreated MBC patients, all showing remarkably high response rates and exceptional tolerability. In randomized phase III trials, the
paclitaxel and
gemcitabine combination showed significant improvements in objective responses, time to progression and overall survival, as compared to
paclitaxel monotherapy, whereas the
docetaxel and
gemcitabine doublet demonstrated equal efficacy and better tolerability, as compared to
docetaxel plus
capecitabine. In addition to standard threeweekly dosing regimens, alternative schedules of administration of
taxanes and
gemcitabine doublets (weekly, twoweekly) might deserve further investigation due to their potential usefulness in reducing pharmacological toxicity while maintaining or increasing dose-intensity and clinical efficacy. Furthermore, uncertainty exists on which
taxane should be preferred in combination with
gemcitabine, since no head-to-head comparison between
paclitaxel-
gemcitabine and
docetaxel-
gemcitabine has been performed so far. Ongoing trials will address these issues and future investigations will also include the evaluation of
bevacizumab, the
monoclonal antibody targeted against
vascular endothelial growth factor (
VEGF), in combination with
taxanes and
gemcitabine doublets.