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

Abstract

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.

Evaluation of Docetaxel vs. Tamoxifen in Combined Therapies Based on Overall Survival Rate (OSR) Endpoint among Female Breast Cancer Patients

“…The combined cancer drug used with either Docetaxel or Tamoxifen serve some clinical purposes, which include resistance management among patients, and enhancement of efficacy. Lee et al [13] found out that Capecitabine was more effective with Docetaxel in combined therapies (17% Pathological complete response (pCR)) among Hormone Receptor (HR)-positive breast cancer than combined therapy of doxorubicin and cyclophosphamide (3% pCR). In the combined therapy of TAM with VOR, VOR worked with TAM to manage hormone resistance among estrogen response (ER)-positive metastatic breast cancer [8].…”

Capecitabine in Combination with Novel Targeted Agents in the Management of Metastatic Breast Cancer: Underlying Rationale and Results of Clinical Trials

“…(Tables 1-4 [9, provide an overview of trials involving capecitabine.) Combinations of capecitabine with standard chemotherapeutic regimens are still being actively investigated (Table 1 [9, [21][22][23][24][25][26][27] provides a summary of data from randomized clinical trials involving capecitabine with other chemotherapeutic agents) along with an increasing number of studies examining the use of capecitabine with newer targeted therapies ( …”

“…Although evaluation of combinations of standard chemotherapeutic agents is continuing and wide ranging, with more than two dozen such trials ongoing [41], the present discussion reviews in detail only the completed pivotal trials for the established combination with docetaxel, together with some recent developments in taxane-based combination therapy. A list of other completed randomized trials evaluating capecitabine and chemotherapeutic agents in combination is presented in Table 1 [9, [21][22][23][24][25][26][27]. (For additional reviews of this topic, see O'Shaughnessy [2] and Fumoleau and Cameron [45].…”

“…Another recent study of capecitabine plus taxane therapy [22] (Table 1) has yielded favorable response rates in the neoadjuvant setting. In a phase III trial involving 204 patients, Lee et al [22] demonstrated that the capecitabinedocetaxel combination (capecitabine, 1,000 mg/m 2 twice daily, and docetaxel, 75 mg/m 2 , in a 3-week cycle) was superior to standard regimens of doxorubicin plus cyclophosphamide given preoperatively for locally advanced disease.…”

“…In a phase III trial involving 204 patients, Lee et al [22] demonstrated that the capecitabinedocetaxel combination (capecitabine, 1,000 mg/m 2 twice daily, and docetaxel, 75 mg/m 2 , in a 3-week cycle) was superior to standard regimens of doxorubicin plus cyclophosphamide given preoperatively for locally advanced disease. The taxane-capecitabine combination resulted in an objective response rate of 84%, versus 67% for the standard regimen (p ϭ .0047), and the pathological complete response rates were 23% versus 10%; comparable tolerability and quality-of-life assessments were seen for the two treatment regimens.…”