Sequential dose-dense doxorubicin, paclitaxel, and cyclophosphamide for resectable high-risk breast cancer: Feasibility and efficacy

Purpose: Dose-dense chemotherapy is predicted to be a superior treatment pl an. Therefore, we studied dose-dense doxorubicin, paclitaxel, and cyclophos phamide (A --> T --> C) as adjuvant therapy. Methods: Patients with resected breast cancer involving four or more ipsila teral axillary lymph nodes were treated with nine cycles of chemotherapy, u sing 14-day intertreatment intervals. Doses were as follows: doxorubicin 90 mg/m(2) x 3, then paclitaxel 250 mg/m(2)/24 hours x 3, and then cyclophosp hamide 3.0 g/m(2) x 3; all doses were given with subcutaneous injections of 5 mu g/kg granulocyte colony-stimulating factor on days 3 through 10. Amen orrheic patients with hormone receptor-positive tumors received tamoxifen 2 0 mg/day for 5 years. Patients treated with breast conservation, those with 10 or more positive nodes, and those with tumors larger than 5 cm received radiotherapy. Results: Between March 1993 and June 1994, we enrolled 42 patients. The med ian age was 46 years (range, 29 to 63 years), the median number of positive lymph nodes was eight (range, four ta 25), and the median tumor size was 3 .0 cm (range, 0 to 11.0 cm). The median intertreatment interval was 14 days (range, 13 to 36 days), and the median delivered dose-intensity exceeded 9 2% of the planned dose-intensity for all three drugs. Hospital admission wa s required for 29 patients (69%), and 28 patients (67%) required blood prod uct transfusion. No treatment-related deaths or cardiac toxicities occurred . Doxorubicin was dose-reduced in four patients (10%) and paclitaxel was re duced in eight (20%). At a median follow-up from surgery of 48 months (rang e, 3 to 57 months), nine patients (19%) had relapsed, the actuarial disease -free survival rate was 78% (95% confidence interval, 66% to 92%), and four patients (10%) had died of metastatic disease. Conclusion: Dose-dense sequential adjuvant chemotherapy with doxorubicin, p aclitaxel, and cyclophosphamide (A --> T --> C) is feasible and promising. Several ongoing phase III trials are evaluating this approach. J Clin Oncol 17:93-100. (C) 1999 by American Society of Clinical Oncology.