Sequential dose-dense 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel in patients with early breast cancer with four or more positive lymph nodes

Aim. The aim of present study was to investigate the feasibility of a densified sequence of FEC75 (5-fluorouracil 600 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide 600 mg/m(2)) and docetaxel 100 mg/m(2) (D-100) in patients with primary operable high-risk breast cancer. Methods. Fifty-one consecutive patients with resectable breast cancer and 4 or more positive axillary lymph nodes were enrolled. After a common regimen of 4 cycles of FEC75 given every 14 days, patients received 4 cycles of D-100 every 14 days. Prophylactic granulocyte colony-stimulating factor was administered subcutaneously at 5 mg/kg daily from days 5 to 10 to each patient. Results. The primary endpoint was the proportion of subjects receiving at least 85% of the relative dose intensity (rDI) both in the FEC and docetaxel parts of the regimen. In view of the high percentage of grade 3-4 skin toxicity (32%) observed in the first 25 patients (Group A) during D-100 treatment, it was decided to continue the study using a docetaxel dose reduced by 15% (85 mg/m(2); D-85). This second group of 26 patients was defined as Group B. Of the total 51 patients, 38 (75%) received docetaxel rDI >= 85%, 23/26 patients (88.5%) and 15/25 patients (60.0%) in Group B and Group A, respectively. The observed grade 3-4 hematological and nonhematological toxicities were in line with data from the literature. The only significant difference was the higher percentage of grade 3-4 skin toxicity experienced with D100. Conclusion. This study failed to demonstrate the feasibility of a dose-dense FEC-D regimen with docetaxel 100 mg/m(2). Docetaxel 85 mg/m(2) seems to allow a higher rDI than docetaxel 100 mg/m(2) but this should be confirmed in a larger cohort of patients.