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Sequential Dose-Dense Doxorubicin, Paclitaxel, and Cyclophosphamide for Resectable High-Risk Breast Cancer: Feasibility and Efficacy

From the Breast and Gynecologic Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Clifford Hudis, MD, MSKCC, 1275 York Ave, Box 206, New York, NY 10024; Email hudisc{at}mskcc.org

PURPOSE: Dose-dense chemotherapy is predicted to be a superior treatment plan. Therefore, we studied dose-dense doxorubicin, paclitaxel, and cyclophosphamide (A T C) as adjuvant therapy.

METHODS: Patients with resected breast cancer involving four or more ipsilateral axillary lymph nodes were treated with nine cycles of chemotherapy, using 14-day intertreatment intervals. Doses were as follows: doxorubicin 90 mg/m² x 3, then paclitaxel 250 mg/m²/24 hours x 3, and then cyclophosphamide 3.0 g/m² x 3; all doses were given with subcutaneous injections of 5 µg/kg granulocyte colony-stimulating factor on days 3 through 10. Amenorrheic patients with hormone receptor-positive tumors received tamoxifen 20 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 median age was 46 years (range, 29 to 63 years), the median number of positive lymph nodes was eight (range, four to 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 92% of the planned dose-intensity for all three drugs. Hospital admission was required for 29 patients (69%), and 28 patients (67%) required blood product transfusion. No treatment-related deaths or cardiac toxicities occurred. Doxorubicin was dose-reduced in four patients (10%) and paclitaxel was reduced in eight (20%). At a median follow-up from surgery of 48 months (range, 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, paclitaxel, and cyclophosphamide (A T C) is feasible and promising. Several ongoing phase III trials are evaluating this approach.

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