Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer
Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer
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DOI：
10.1093/jnci/djn151
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发表时间：
2008-06-04
影响因子：
10.3
通讯作者：
Manuel Lopez-Vega, Jose
中科院分区：
文献类型：
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作者：
Martin, Miguel;Rodriguez-Lescure, Alvaro;Manuel Lopez-Vega, Jose
背景 紫杉烷类药物是治疗转移性乳腺癌最有效的药物之一，因此也在辅助治疗中进行了研究。 方法 乳腺癌手术后，淋巴结阳性疾病的女性被随机分配接受氟尿嘧啶、表柔比星和环磷酰胺 (FEC) 治疗，或先接受 FEC 治疗，然后每周接受紫杉醇治疗 (FEC-P)。研究的主要终点——5 年无病生存 (DFS)——通过 Kaplan-Meier 分析进行评估。次要终点包括总体生存率以及临床和分子标记物（通过免疫组织化学检测激素受体和通过荧光原位杂交检测 HER2）标记物的预后和预测价值的分析。使用 DFS 的多变量 Cox 比例风险模型评估以下协变量的关联和相互作用：年龄、绝经状态、肿瘤大小、淋巴结状态、化疗类型、肿瘤大小、阳性淋巴结、HER2 状态和激素受体状态。所有统计检验均为双向。 结果 在 1246 名符合条件的患者中，FEC-P 组的 5 年 DFS 估计率为 78.5%，FEC 组为 72.1%（差异 = 6.4%，95% 置信区间 [CI] = 1.6% 至 11.2%；P = .006）。与 FEC 治疗相比，FEC-P 治疗使复发风险降低 23%（FEC-P 组 614 例患者中有 146 例复发，FEC 组 632 例患者中有 193 例复发，风险比 [HR] = 0.77，95% CI = 0.62 至 0.95；P = 0.022），死亡风险降低 22% （分别有 73 人和 95 人死亡， HR = 0.78，95% CI = 0.57 至 1.06； P = .110）。在对肿瘤样本进行集中分析的 928 名患者中，化疗类型（FEC 与 FEC-P）（P = .017）、受累腋窝淋巴结数量（P < .001）、肿瘤大小（P = .020）、激素受体状态（P = .004）和 HER2 状态（P = .006）均与 DFS 相关。我们发现 HER2 状态与紫杉醇治疗之间或激素受体状态与紫杉醇治疗之间没有统计学上显着的相互作用。 结论 在可手术乳腺癌患者中，与 FEC 作为辅助治疗相比，FEC-P 治疗在统计学上显着降低了复发风险。
Background Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting.Methods After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided.Results Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment.Conclusions Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.