Gemcitabine, epirubicin, and paclitaxel combinations in advanced breast cancer

Strategies to improve outcome in metastatic breast cancer include the first-line use of combinations of optimal doses of active agents, with the goal being to improve complete response rates and thus long-term survival. Although prior studies of anthracycline/taxane combinations generally have shown improved response rates and progression-free survival in comparison with single-agent regimens or anthracycline/cyclophosphamide-containing combinations, the data have not consistently demonstrated improved overall survival; indeed, they have yielded generally disappointing complete response rates. We evaluated the combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), epirubicin, and paclitaxel (GET) based on the hypothesis that epirubicin/paclitaxel is best suited for achieving delivery of optimal doses, and the addition of gemcitabine (which exhibits good single-agent activity with a favorable toxicity profile) will increase activity. In a phase II trial of 36 patients, the GET regimen produced reasonable toxicity and was associated with a 92% response rate, including complete responses in 31% of patients. The overall response rate increased to 97%, including complete responses in 41% of patients, with high-dose consolidation chemotherapy in 25 patients. A trial comparing GET with epirubicin/paclitaxel as first-line treatment in more than 600 patients with metastatic breast cancer has been initiated, with survival as the primary end point. Another large-scale trial is being planned to compare the GET regimen with an anthracycline/cyclophosphamide/paclitaxel combination in patients with early stage high-risk breast cancer.