Poole Christopher J, Earl Helena M, Hiller Louise, Dunn Janet A, Bathers Sarah, Grieve Robert J, Spooner David A, Agrawal Rajiv K, Fernando Indrajit N, Brunt A Murray, O'Reilly Susan M, Crawford S Michael, Rea Daniel W, Simmonds Peter, Mansi Janine L, Stanley Andrew, Harvey Peter, McAdam Karen, Foster Liz, Leonard Robert C F, Twelves Christopher J
Cancer Research UK Clinical Trials Unit, Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom.
N Engl J Med. 2006 Nov 2;355(18):1851-62. doi: 10.1056/NEJMoa052084.
The National Epirubicin Adjuvant Trial (NEAT) and the BR9601 trial examined the efficacy of anthracyclines in the adjuvant treatment of early breast cancer.
In NEAT, we compared four cycles of epirubicin followed by four cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) with six cycles of CMF alone. In the BR9601 trial, we compared four cycles of epirubicin followed by four cycles of CMF, with eight cycles of CMF alone every 3 weeks. The primary end points were relapse-free and overall survival. The secondary end points were adverse effects, dose intensity, and quality of life.
The two trials included 2391 women with early breast cancer; the median follow-up was 48 months. Relapse-free and overall survival rates were significantly higher in the epirubicin-CMF groups than in the CMF-alone groups (2-year relapse-free survival, 91% vs. 85%; 5-year relapse-free survival, 76% vs. 69%; 2-year overall survival, 95% vs. 92%; 5-year overall survival, 82% vs. 75%; P<0.001 by the log-rank test for all comparisons). Hazard ratios for relapse (or death without relapse) (0.69; 95% confidence interval [CI], 0.58 to 0.82; P<0.001) and death from any cause (0.67; 95% CI, 0.55 to 0.82; P<0.001) favored epirubicin plus CMF over CMF alone. Independent prognostic factors were nodal status, tumor grade, tumor size, and estrogen-receptor status (P<0.001 for all four factors) and the presence or absence of vascular or lymphatic invasion (P=0.01). These factors did not significantly interact with the effect of epirubicin plus CMF. The overall incidence of adverse effects was significantly higher with epirubicin plus CMF than with CMF alone but did not significantly affect the delivered-dose intensity or the quality of life.
Epirubicin plus CMF is superior to CMF alone as adjuvant treatment for early breast cancer. (ClinicalTrials.gov number, NCT00003577 [ClinicalTrials.gov].).
国家表柔比星辅助治疗试验（NEAT）和BR9601试验研究了蒽环类药物在早期乳腺癌辅助治疗中的疗效。
在NEAT试验中，我们将四个周期的表柔比星序贯四个周期的环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF）方案与单纯六个周期的CMF方案进行了比较。在BR9601试验中，我们将四个周期的表柔比星序贯四个周期的CMF方案与每3周单纯八个周期的CMF方案进行了比较。主要终点为无复发生存期和总生存期。次要终点为不良反应、剂量强度和生活质量。
两项试验共纳入2391例早期乳腺癌女性患者；中位随访时间为48个月。表柔比星联合CMF组的无复发生存率和总生存率显著高于单纯CMF组（2年无复发生存率，91%对8%；5年无复发生存率，76%对69%；2年总生存率，95%对92%；5年总生存率，82%对75%；所有比较经对数秩检验P<0.001）。复发（或无复发死亡）的风险比（0.69；95%置信区间[CI]，0.58至0.82；P<0.001）和任何原因导致的死亡风险比（0.67；95%CI，0.55至0.82；P<0.001）表明，表柔比星联合CMF优于单纯CMF。独立预后因素为淋巴结状态、肿瘤分级、肿瘤大小和雌激素受体状态（所有四个因素P<0.001）以及是否存在血管或淋巴管侵犯（P=0.01）。这些因素与表柔比星联合CMF的疗效无显著相互作用。表柔比星联合CMF组的不良反应总发生率显著高于单纯CMF组，但对实际给药剂量强度或生活质量无显著影响。
表柔比星联合CMF作为早期乳腺癌的辅助治疗优于单纯CMF。（ClinicalTrials.gov编号，NCT00003577[ClinicalTrials.gov]。）
