Overview of gemcitabine activity in advanced breast cancer

Gemcitabine, an antimetabolite that is incorporated as a triphosphate into DNA, is active as a single agent in first- and subsequent-line treatment of breast cancer, with an overall objective response rate of 26%. It is relatively well tolerated, and its dose-limiting toxicity has usually been neutropenia. Gemcitabine has proven active in combination with paclitaxel and, on this basis, a phase III trial showed a significantly higher response rate than paclitaxel alone (39.3% v 25.6%). The combination also showed a significantly longer median time to progression (5.2 v 2.9 months) and significantly improved median overall survival time (18.5 v 15.8 months). Apart from neutropenia, there was no significant increase in toxicity for the combination. Gemcitabine has also been shown to be active in combination with docetaxel, and a phase III trial has shown that gemcitabine plus docetaxel is as effective as capecitabine plus docetaxel, but with significantly less nonhematologic toxicity. Two-week schedules of gemcitabine plus paclitaxel or docetaxel are currently being investigated, as are combinations with paclitaxel plus trastuzumab, and paclitaxel plus anthracyclines. These results have prompted ongoing trials of gemcitabine in early breast cancer as neoadjuvant and adjuvant therapy.