A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer

We aimed to determine the efficacies of a non-anthracycline-containing regimen, docetaxel/capecitabine (TX), in comparison with an anthracycline-containing regimen, doxorubicin/cyclophosphamide (AC), as primary chemotherapy for node-positive early stage breast cancer. In this phase-III single center randomized study, we randomized 209 women with axillary node positive, stage II/III breast cancer to receive four cycles of either TX or AC followed by surgery and cross-over to the other treatment as an adjuvant therapy. The primary endpoint was tumor pathologic complete response (pCR). Clinical response rates, toxicity profiles, disease free survival (DFS), and overall survival were secondary objectives. In total, 204 patients had clinical and radiological evaluation of response, and underwent surgery. Compared with AC, TX increased pCR in primary tumors (21% vs. 10%, respectively, P = 0.024) and clinical response (84% vs. 65%, P = 0.003). TX was associated with less nausea and vomiting, but more stomatitis, diarrhea, myalgia, and skin/nail changes than AC. With a median follow-up of 37 months, there was no significant difference in DFS by treatment groups (P = 0.932). Fewer patients developed recurrence who achieved pCR in lymph node (LN) (P = 0.025; hazard ratio, 0.189; 95% CI, 0.044-0.815) in the multivariate analysis. TX showed superior efficacies to AC with increased pathologic and clinical complete response rates. Although these findings did not translate into a gain in DFS, the patients who achieved pCR in LN developed significantly less recurrence.