5-year results of dose-intensive sequential adjuvant chemotherapy for women with high-risk node-positive breast cancer: A phase II study

Purpose: We conducted a phase II pilot study of dose-intensive adjuvant che motherapy with doxorubicin followed sequentially by high-dose cyclophospham ide to determine the safety and feasibility of this dose-dense treatment an d to estimate the disease-free and overall survival in breast cancer patien ts with four or more involved axillary lymph nodes. patients and Methods: Seventy-three patients received adjuvant treatment wi th four cycles of doxorubicin 75 mg/m(2) as an intravenous bolus every 21 d ays, followed by three cycles of cyclophosphamide 3,000 mg/m(2) every 14 da ys with granulocyte colony-stimulating factor support. Results: Seventy one patients were assessable, and all but two completed al l planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. M edian disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and over-all survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of ac ute myelogenous leukemia or myelodysplastic syndrome have been observed. Conclusion: Our pilot study of doxorubicin followed by cyclophosphamide dem onstrates the safety and feasibility of the sequential dose dense plan. Lon g-term follow-up, although noncomparative, is promising. However, this regi men is associated with a higher incidence of toxicity (and also higher cost s) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose dense approach have been completed but not yet reported. Because the seque ntial plan can decrease overlapping toxicities, it is an appropriate platfo rm for the addition of newer active agents, such as taxanes or monoclonal a ntibodies. (C) 1999 by American Society of Clinical Oncology.