Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer (original) (raw)

2008, New England Journal of Medicine

BACKGROUND-We compared the efficacy of two different taxanes, docetaxel and paclitaxel, given either weekly or every 3 weeks, in the adjuvant treatment of breast cancer. METHODS-We enrolled 4950 women with axillary lymph node-positive or high-risk, lymph node-negative breast cancer. After randomization, all patients first received 4 cycles of intravenous doxorubicin and cyclophosphamide at 3-week intervals and were then assigned to intravenous paclitaxel or docetaxel given at 3-week intervals for 4 cycles or at 1-week intervals for 12 cycles. The primary end point was disease-free survival. RESULTS-As compared with patients receiving standard therapy (paclitaxel every 3 weeks), the hazard ratio for disease-free survival was 1.27 among those receiving weekly paclitaxel (P = 0.006), 1.23 among those receiving docetaxel every 3 weeks (P = 0.02), and 1.09 among those receiving weekly docetaxel (P = 0.29) (with a hazard ratio >1 favoring the groups receiving experimental therapy). As compared with standard therapy, weekly paclitaxel was also associated with improved survival (hazard ratio, 1.32; P = 0.01). An exploratory analysis of a subgroup of patients whose tumors expressed no human epidermal growth factor receptor type 2 protein found similar improvements in disease-free and overall survival with weekly paclitaxel treatment, regardless of hormone-receptor expression. Grade 2, 3, or 4 neuropathy was more frequent with weekly paclitaxel than with paclitaxel every 3 weeks (27% vs. 20%). CONCLUSIONS-Weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with breast cancer. (ClinicalTrials.gov number, NCT00004125.) ADJUVANT CHEMOTHERAPY SUBSTANTIally reduces the risk of recurrence and death among women with operable breast cancer. 1 The addition of a taxane to an anthracycline-containing regimen, whether after or concurrently with anthracycline treatment, further reduces the risk of relapse. Two studies in which patients received four cycles of paclitaxel every 3 weeks after receiving four cycles of doxorubicin and cyclophosphamide every 3 weeks 2,3 established a new standard of care for operable breast cancer and led to regulatory approval of paclitaxel for axillary lymph node-positive breast cancer. Another study demonstrating that concurrent administration of