Weekly paclitaxel in the adjuvant treatment of breast cancer

Abstract

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 odds 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 an odds ratio >1 favoring the groups receiving experimental therapy). As compared with standard therapy, weekly paclitaxel was also associated with improved survival (odds 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 [ClinicalTrials.gov].).

Copyright 2008 Massachusetts Medical Society.

Figures

Figure 1. Disease-free Survival

Panel A shows disease-free survival according to treatment group. Panel B shows the hazard ratios for disease-free survival in the experimental groups as compared with the group receiving standard treatment (paclitaxel every 3 weeks).

Figure 2. Overall Survival

Panel A shows overall survival according to treatment group. Panel B shows the hazard ratios for overall survival in the experimental groups as compared with the group receiving standard treatment (paclitaxel every 3 weeks).

Figure 3. Exploratory Analysis of Disease-free and Overall Survival According to Expression of Human Epidermal Growth Factor Receptor Type 2 (HER2)

Panel A shows the hazard ratios for disease-free survival and Panel B shows the hazard ratios for overall survival according to HER2 expression in the experimental groups as compared with the group receiving paclitaxel every 3 weeks.

Figure 4. Exploratory Analysis of Disease-free and Overall Survival According to Expression of Hormone Receptors (HR)

The figure shows the hazard ratios for disease-free and overall survival the group receiving weekly paclitaxel in as compared with the group receiving paclitaxel every 3 weeks among patients with HER2-negative disease according to whether the disease was positive or negative for hormone receptors.