Phase II Study of Feasibility of Dose-Dense FEC Followed by Alternating Weekly Taxanes in High-Risk, Four or More Node-Positive Breast Cancer

Purpose: To develop a potentially superior adjuvant chemotherapy regimen, we conducted a pilot study of dose-dense 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by weekly alternating taxanes. The primary objective was to determine the feasibility of the regimen; the secondary objective was to estimate the disease-free and overall survival. Experimental Design: Patients with ≥4 node-positive breast cancer were studied. Treatment consisted of FEC at 500/100/500 mg/m2, respectively, ×6 at two-week intervals with granulocyte colony-stimulating factor, followed by weekly paclitaxel (80 mg/m2) alternating with docetaxel (35 mg/m2) ×18. Results: Between November 2001 and January 2003, 44 patients were enrolled. Median age was 46 years (range, 26–63 years), median number of positive nodes was 9 (range, 4–32), and median tumor size was 2.5 cm (range, 0.6–11.0 cm). Because of unexpected toxicities, the study was stopped when 17 (39%) had fully completed all of the planned treatment. Two of 17 (12%) developed grade 4 pericardial/grade 3 bilateral pleural effusions at treatment completion; both required pericardial window. The remaining patients were treated with taxanes using one of several standard dose and schedule combinations. Furthermore, 4 of 44 (9%) developed pneumonitis attributed to the FEC regimen. Hospital admissions were required for 12 of 44 (27%); 3 of 44 (7%) required blood transfusions. There were no treatment related deaths. Median disease-free and overall survival will not be estimatable because of early closure of study. Conclusion: FEC ×6 at 2-week intervals followed by 18 weeks of alternating taxanes is not feasible at the doses tested. Other strategies are needed to improve adjuvant systemic chemotherapy.