Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
J Natl Cancer Inst. 2011 Oct 19;103(20):1529-39. doi: 10.1093/jnci/djr351. Epub 2011 Sep 15.
The most appropriate timing of chemotherapy and hormone therapy administration is a critical issue in early breast cancer patients. The purpose of our study was to compare the efficacy of concurrent vs sequential administration of adjuvant chemotherapy and tamoxifen.
Women with node-positive primary breast cancer were randomly assigned to receive tamoxifen (20 mg/d for 5 years) during (concurrent arm) or after (sequential arm) adjuvant chemotherapy. Chemotherapy consisted of alternating regimens of cyclophosphamide, epidoxorubicin, and 5-fluorouracil and cyclophosphamide, methotrexate, and 5-fluorouracil every 21 days for a total of 12 cycles. The primary endpoint was overall survival (OS), and secondary endpoints were toxic effects and disease-free survival (DFS). No provision for interim analyses was made in the original study protocol. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models, adjusted for age, menopausal status, tumor stage, and lymph node and hormone receptor status, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.
From 1985 to 1992, 431 patients were randomly assigned and studied according to the intention-to-treat principle. After a maximum of 15.4 years of follow-up (median 12.3 years), the estimated actuarial 10-year OS was equivalent for the two study arms (concurrent arm: 111 patients, 66%, 95% CI = 59% to 72%; sequential arm: 114 patients, 65%, 95% CI = 59% to 72%, P = .86). No differences in DFS and toxic effects were evident. Four interim analyses were performed, but no alpha error adjustment was necessary because of the largely negative results of this final analysis (sequential vs concurrent arm: HR of death = 1.06, 95% CI = 0.78 to 1.44, P = .76; HR of relapse = 1.16, 95% CI = 0.88 to 1.52, P = .36).
No statistically significant differences in OS, DFS, and toxic effects between concurrent and sequential adjuvant chemo- and hormone therapies were observed. Our study does not support the superiority of one schedule of chemo- and hormone-therapy administration over the other. However, because of the limited statistical power of the study, these results must be considered with caution.
化疗和激素治疗的最佳时机是早期乳腺癌患者的一个关键问题。我们的研究目的是比较辅助化疗和他莫昔芬同时与序贯给药的疗效。
淋巴结阳性的原发性乳腺癌女性患者被随机分配接受他莫昔芬（5 年 20mg/d）治疗[同时给药组（concurrent arm）]或辅助化疗后（序贯给药组（sequential arm））。化疗方案为环磷酰胺、表阿霉素和 5-氟尿嘧啶每 21 天交替使用，共 12 个周期；环磷酰胺、甲氨蝶呤和 5-氟尿嘧啶也每 21 天交替使用，共 12 个周期。主要终点是总生存期（OS），次要终点是毒性作用和无病生存期（DFS）。原始研究方案中未规定中期分析。生存曲线采用 Kaplan-Meier 法估计。多变量 Cox 回归模型，根据年龄、绝经状态、肿瘤分期、淋巴结和激素受体状态进行调整，用于估计风险比（HR）和 95%置信区间（CI）。所有统计检验均为双侧检验。
1985 年至 1992 年，431 例患者按意向治疗原则随机分配并进行研究。在最长 15.4 年的随访（中位随访 12.3 年）后，根据估计的生存率，两组之间的 10 年估计生存率无差异（同时给药组：111 例患者，66%，95%CI=59%至 72%；序贯给药组：114 例患者，65%，95%CI=59%至 72%，P=0.86）。DFS 和毒性作用无显著差异。进行了 4 次中期分析，但由于最终分析的结果大多为阴性，因此无需进行 alpha 错误调整（序贯 vs 同时给药：死亡风险 HR=1.06，95%CI=0.78 至 1.44，P=0.76；复发风险 HR=1.16，95%CI=0.88 至 1.52，P=0.36）。
同时与序贯辅助化疗和激素治疗的 OS、DFS 和毒性作用无统计学差异。我们的研究不支持一种化疗和激素治疗方案优于另一种方案。然而，由于研究的统计效力有限，这些结果必须谨慎考虑。
