Gemcitabine and docetaxel in metastatic and neoadjuvant treatment of breast cancer

Treatment advances in breast cancer continue to revolve around the development of novel agents and combinations, with the major therapeutic goal of these investigational treatment strategies revolving around the improvement of response rates, delaying the time to disease progression, palliation of symptoms, and improving quality of life. Recognized as one of the most active single agents in breast cancer, docetaxel has shown remarkable activity in combination with gemcitabine. Gemcitabine, a novel S-phase specific cytidine nucleoside analogue of deoxycytidine with broad antitumor activity, has evident single-agent activity in the treatment of breast cancer. Its novel mechanism of action, in addition to its generally favorable toxicity profile and largely nonoverlapping toxicities, has facilitated its further development in combination regimens, particularly with the taxanes. Several phase I and II trials have reported impressive activity for the gemcitabine/docetaxel doublet with the suggestion of clinical synergism between these two agents. Additional phase II trials have focused on optimizing dosing and schedule schemas with the demonstration of impressive efficacy with acceptable toxicity with the biweekly administration. Unmistakably, these trials collectively show clear improvements for the gemcitabine/docetaxel doublet over that reported for the single-agent activity of the taxanes in metastatic breast cancer. These favorable findings have resulted in the further investigation of and incorporation of gemcitabine in neoadjuvant treatment strategies. From its favorable therapeutic index to substantial efficacy in combination with docetaxel, gemcitabine remains a rational and important addition to the treatment armamentarium of breast cancer.