Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer
Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer
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DOI：
10.1200/jco.2003.02.063
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发表时间：
2003-03-15
影响因子：
45.3
通讯作者：
Norton, L
中科院分区：
文献类型：
--
作者：
Henderson, IC;Berry, DA;Norton, L
目的：本研究旨在确定增加阿霉素剂量或在乳腺癌患者的标准辅助化疗方案中加入紫杉醇是否会延长复发和生存时间。手术治疗后，3,121名可手术乳腺癌和淋巴结受累的女性被随机分配接受环磷酰胺（C），600 μ g/m2，多柔比星（A）60、75或90 μ g/m2，连续4个周期，然后不进一步治疗或紫杉醇175 μ g/m2治疗4个周期。94%的激素受体阳性肿瘤患者接受了他莫昔芬治疗。随机分配至60、75和90 mg/m2组的患者5年无病生存率分别为69%、66%和67%。在CA基础上加用紫杉醇的复发风险降低17%（校正Wald chi（2）P =.0023;未校正Wilcoxon P =.0011），死亡风险降低18%（校正P =.0064;未校正P = .0098）。5年时，单独CA或CA加紫杉醇治疗后的无病生存率（+/- SE）分别为65%（+/- 1）和70%（+/- 1），总生存率分别为77%（+/- 1）和80%（+/- 1）。在方案定义的亚组中，加用紫杉醇的效果无显著差异，但在计划外亚组分析中，CA加用紫杉醇与单独CA相比的风险比为0.72（95%置信区间，0.59至0.86）对于那些雌激素受体阴性的肿瘤和只有0.91（95%置信区间，0.78至1.07）的雌激素受体阳性肿瘤患者，几乎所有的人都接受了辅助他莫昔芬。从增加四个周期的紫杉醇的额外毒性一般moderate.Conclusion：除了四个周期的紫杉醇完成后，CA的标准课程提高了早期乳腺癌患者的无病生存和总生存。J Clin Oncol 21：976-983. (C)2003年，美国临床肿瘤学会。
Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival.Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 Mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 Mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 Mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors.Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%,66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P = .0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% ( +/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest.Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer. J Clin Oncol 21:976-983. (C) 2003 by American Society of Clinical Oncology.