Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: Final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study

AC-紫杉烷方案与不含AC方案方案以及紫杉醇与多西他赛在淋巴结阳性乳腺癌患者中的比较:美国国家乳腺癌外科辅助治疗研究02试验(一项随机对照3期研究)的最终结果

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Abstract

BACKGROUND: In postoperative patients with breast cancer, the combination of an anthracycline and cyclophosphamide (AC) followed by a taxane is a standard regimen. In the current study, the authors examined whether AC could be safely omitted, and compared the effectiveness of paclitaxel versus docetaxel. METHODS: Female postoperative patients with axillary lymph node-positive breast cancer were eligible for enrollment in this phase 3, open-label, randomized controlled trial at 84 centers in Japan. Patients were randomized to 4 cycles of doxorubicin at a dose of 60 mg/m(2) and cyclophosphamide at a dose of 600 mg/m(2) (AC) followed by 4 cycles of paclitaxel at a dose of 175 mg/m(2) (ACpT) or AC followed by 4 cycles of docetaxel at a dose of 75 mg/m(2) (ACdT), or 8 cycles of paclitaxel (PTx) or docetaxel (DTx) every 3 weeks. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival adverse events. The authors adopted a 2 × 2 factorial design to examine the AC containing-regimens (ACpT and ACdT) versus the AC free-regimens (PTx and DTx), and the paclitaxel-containing regimens (ACpT and PTx) versus the docetaxel-containing regimens (ACdT and DTx). RESULTS: Of 1060 patients, 1049 were treated and included in the intention-to-treat population. The DFS results did not demonstrate noninferiority between the AC-containing and the AC-free regimens (hazard ratio [HR], 1.19; 95% confidence interval [95% CI], 0.982-1.448 [P(noninferiority)  = .30]). Better outcomes were noted in patients treated with the docetaxel-containing regimens compared with the paclitaxel-containing regimens with respect to DFS (HR, 0.72; 95% CI, 0.589-0.875 [P = .0008]) and overall survival (HR, 0.75; 95% CI, 0.574-0.980 [P = .035]). Neutropenia, nausea, and vomiting were found to occur more often in the AC-containing arms, whereas the incidence of edema was greater in the docetaxel-containing treatment arms. CONCLUSIONS: Noninferiority in DFS was not demonstrated between the AC-containing and AC-free regimens. Compared with a similar regimen of paclitaxel, docetaxel appeared to increase the DFS. Cancer 2017;123:759-68. © 2016 American Cancer Society.

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