Phase III Trial Evaluating Weekly Paclitaxel Versus Docetaxel in Combination With Capecitabine in Operable Breast Cancer

We investigated whether capecitabine and docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide (FEC) or weekly paclitaxel (WP) followed by FEC would improve relapse-free survival (RFS) in operable breast cancer. In this single-institution study, patients with clinical stages I to IIIC breast cancer were randomly assigned on a 1:1 basis to WP 80 mg/m(2) for 12 weeks followed by fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-100) every 3 weeks for four cycles or docetaxel 75 mg/m(2) on day 1 and capecitabine (XT) 1,500 mg/m(2) on days 1 through 14 every 3 weeks for four cycles followed by FEC for four cycles and stratified by timing of chemotherapy (preoperative v adjuvant). Accrual was stopped short of 930 patients on the basis of a Bayesian predictive calculation that additional accrual would be unlikely to change the qualitative comparison of the two regimens. After enrollment of 601 patients and a median follow-up of 50 months, we observed no improvement in RFS between XT (87.5%; 95% CI, 82.7% to 91.1%) and WP (90.7%; 95% CI, 86.4% to 93.7%; P = .51). In the preoperative group, the pathologic complete response rate was 19.8% and 16.4% in the XT and WP arms, respectively (P = .45). Rates of breast-conserving surgery were similar between the two groups (P = .48). The XT arm had a significantly higher incidence of stomatitis (P < .001), hand-foot syndrome (P < .001), and neutropenic infection (P < .001). There was no difference in efficacy between WP and XT as used in this randomized phase III trial. XT was associated with higher GI, skin, and neutropenic-related toxicities.