The docetaxel and gemcitabine combination is an active regimen as salvage therapy in taxane-resistant or taxane-refractory patients with metastatic breast cancer (MBC). We recently conducted a phase II study administering this combination to patients with MBC after docetaxel failure, with remarkably high response rates that could be attributed to an in vivo synergism between the two drugs. Women with MBC who were refractory or resistant to docetaxel monotherapy as first- or second-line treatment were recruited. Patients with progressive or stable disease after receiving a minimum of four cycles of docetaxel received gemcitabine 900 mg/m(2) on days 1 and 8 plus docetaxel 100 mg/m(2)on day 8, every 3 weeks. Forty-six percent of patients responded (three complete responses, 20 partial responses), while 28% had stable disease and 26% had progressive disease. Median duration of response was 6.07 +/- 2.43 months. Neutropenia was the only grade 4 toxicity, and reported in seven patients. Other grade 3 toxicities included neutropenia (12 patients), thrombocytopenia (seven patients), and anemia (one patient), while nonhematologic toxicities were easily manageable. These data outline the importance of a rational combination of existing, active chemotherapeutic agents for MBC, and broadens our perspectives for more effective combination regimens in various solid tumors in the future.