Leonard Robert C F, Lind Michael, Twelves Christopher, Coleman Robert, van Belle Simon, Wilson Charles, Ledermann Jonathan, Kennedy Ian, Barrett-Lee Peter, Perren Timothy, Verrill Mark, Cameron David, Foster Elizabeth, Yellowlees Ann, Crown John
South West Wales Cancer Institute, Singleton Hospital, Swansea, Wales, UK.
J Natl Cancer Inst. 2004 Jul 21;96(14):1076-83. doi: 10.1093/jnci/djh188.
BACKGROUND: Breast cancer patients with four or more positive axillary lymph nodes who are treated with conventional adjuvant therapy have a poor prognosis. In uncontrolled studies, high-dose chemotherapy produced much better results than conventional therapy. We compared the benefits of a single cycle of high-dose chemotherapy and the benefits of conventional chemotherapy in patients with high-risk breast cancer in a prospective, unblinded, randomized trial. METHODS: Between February 23, 1995, and June 29, 1999, 605 patients with breast cancer who had four or more positive lymph nodes were randomly assigned to treatment (307 to high-dose therapy and 298 to conventional therapy). The conventional chemotherapy regimen was four cycles of doxorubicin (75 mg/m2) followed by eight cycles of CMF (cyclophosphamide [600 mg/m2], methotrexate [50 mg/m2], and 5-fluorouracil [600 mg/m2]), all given intravenously on day 1 of a 21-day cycle. The high-dose regimen was four cycles of doxorubicin (75 mg/m2), followed by a single cycle of intermediate-dose cyclophosphamide (4000 mg/m2) supported by filgrastim (300 microg/day) for up to 10 days followed by high-dose cyclophosphamide (6000 mg/m2) and thiotepa (800 mg/m2). Peripheral blood progenitor cells were harvested by leukapheresis after treatment with cyclophosphamide and filgrastim and then re-infused after the high-dose cycle. Log-rank tests were used to compare survival rates. All statistical analyses were two-sided. RESULTS: At a median follow-up of 6 years, no statistically significant differences were detected between the arms in 5-year relapse-free survival (high-dose arm = 57%, 95% confidence interval [CI] = 51% to 63%; conventional-dose arm = 54%, 95% CI = 48% to 61% (P =.73) or in 5-year overall survival (high-dose arm = 62%, 95% CI = 56% to 68%; conventional-dose arm = 64%, 95% CI = 57% to 70%) (P =.38). CONCLUSION: Autograft-supported, high-dose therapy is not superior to conventional chemotherapy in patients with breast cancer who have multiple involved lymph nodes. This conclusion should be viewed in the context of improving the success of conventional chemotherapy.
背景：接受传统辅助治疗的腋窝淋巴结有四个或更多转移灶的乳腺癌患者预后较差。在非对照研究中，高剂量化疗的效果比传统治疗好得多。我们在一项前瞻性、非盲法、随机试验中比较了单周期高剂量化疗和传统化疗对高危乳腺癌患者的疗效。 方法：在1995年2月23日至1999年6月29日期间，605例腋窝淋巴结有四个或更多转移灶的乳腺癌患者被随机分配接受治疗（307例接受高剂量治疗，298例接受传统治疗）。传统化疗方案为四个周期的阿霉素（75mg/m²），随后是八个周期的CMF（环磷酰胺[600mg/m²]、甲氨蝶呤[50mg/m²]和5-氟尿嘧啶[600mg/m²]），均在21天周期的第1天静脉给药。高剂量方案为四个周期的阿霉素（75mg/m²），随后是一个周期的中剂量环磷酰胺（4000mg/m²），由非格司亭（300μg/天）支持，持续10天，随后是高剂量环磷酰胺（6000mg/m²）和噻替派（800mg/m²）。在用环磷酰胺和非格司亭治疗后，通过白细胞分离术采集外周血祖细胞，然后在高剂量周期后重新注入。采用对数秩检验比较生存率。所有统计分析均为双侧检验。 结果：在中位随访6年时，两组在5年无复发生存率（高剂量组=57%，95%置信区间[CI]=51%至63%；传统剂量组=54%，95%CI=48%至61%（P=0.73））或5年总生存率（高剂量组=62%，95%CI=56%至68%；传统剂量组=64%，95%CI=57%至70%）（P=0.38）方面均未检测到统计学上的显著差异。 结论：在有多枚受累淋巴结的乳腺癌患者中，自体移植支持的高剂量治疗并不优于传统化疗。这一结论应结合提高传统化疗成功率的背景来考虑。
J Natl Cancer Inst. 2005-12-7
Cancer Biol Med. 2021-8-27
J Exp Clin Cancer Res. 2013-11-11
Zotero 插件