1. ¹Department of Gynecology/Obstetrics, University Medicine Berlin, Charité Campus Mitte, Schumannstr. 20/21, Berlin 10117, Germany
2. ²Krankenhaus Lichtenberg, Klinik für Frauenheilkunde, Fanningerstr. 32, Berlin 10365, Germany
3. ³Evangelisches Krankenhaus Ludwigsfelde-Teltow, Ludwigsfelde GmbH, Albert-Schweitzer-Strastr. 42-44, Ludwigsfelde 14974, Germany
4. ⁴Staedtisches Klinikum Neunkirchen GmbH, Neunkirchen GmbH, Brunnenstr. 20, Neunkirchen/Saar D-66538, Germany
5. ⁵Helios Klinikum Berlin-Buch, Wiltbergstr. 50, Berlin 13125, Germany
6. ⁶Humaine-Klinikum Bad Saarow, Pieskowerstr. 33, Bad Saarow-Pieskow 15526, Germany

Correspondence: Dr S Kümmel, E-mail: sherko.kuemmel@charite.de

Received 7 November 2005; Revised 8 March 2006; Accepted 9 March 2006; Published online 11 April 2006.

Abstract

We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m^-2 plus paclitaxel 175 mg m^-2 in four 14-day cycles, then cyclophosphamide 600 mg m^-2, methotrexate 40 mg m^-2, and fluorouracil 600 mg m^-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 g kg day^-1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m^-2 plus cyclophosphamide 600 mg m^-2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer.