Clinical relevance of different sequencing of doxorubicin and cyclophosphamide, methotrexate, and fluorouracil in operable breast cancer
Clinical relevance of different sequencing of doxorubicin and cyclophosphamide, methotrexate, and fluorouracil in operable breast cancer
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DOI：
10.1200/jco.2004.07.190
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发表时间：
2004-05-01
影响因子：
45.3
通讯作者：
Valagussa, P
中科院分区：
文献类型：
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作者：
Bonadonna, G;Zambetti, M;Valagussa, P
目的 评估不同序列的阿霉素 (DOX) 和环磷酰胺、甲氨蝶呤和氟尿嘧啶 (CMF) 对于有疾病复发风险的可手术乳腺癌患者的临床相关性。患者和方法 20 世纪 80 年代初期启动了两项随机试验。第一项研究针对有 1 至 3 个淋巴结受累的患者，旨在评估每 3 周静脉注射 (IV) CMF 12 个疗程的有效性，对比相同 CMF 方案 8 个疗程，随后接受 4 个疗程全剂量 DOX (CMF-->DOX) 的效果。第二项研究，在涉及三个以上淋巴结的患者中，比较了连续 4 个全剂量 DOX 疗程随后进行 8 个 IV CMF 疗程 (DOX-->CIVF) 与交替使用 2 个疗程的相同 CMF 方案与 1 个疗程的 DOX (CMF/DOX) 总共 12 个疗程。结果 在中位观察 210 个月后，第一项研究中没有记录到统计学上的显着差异。 （无复发生存风险率[HRI，1.06；总生存HR，1.03）。相比之下，与交替方案相比，先给予 DOX，然后给予 CMF 显着降低了疾病复发（HR，0.68；95% Cl，0.54 至 0.87；P =.0017）和死亡（HR，0.74；95% Cl，0.57 至 0.95；P =.018）的风险。复发和 与 CMF 相比死亡。然而，我们的试验中观察到的结果强调，蒽环类佐剂方案的相对优点也可能取决于给药方式，并且必须在适当设计的试验中进行评估，在试验中可以权衡益处的大小和潜在的风险。
Purpose To assess the clinical relevance of different sequences of doxorubicin (DOX) and cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with operable breast cancer at risk of disease relapse.Patients and Methods Two randomized trials were activated in the early 1980s. The first study, in patients with one to three involved nodes, was intended to assess the effectiveness of intravenous (IV) CMF given every 3 weeks for 12 courses versus eight courses of the same CMF regimen followed by four courses of full-dose DOX (CMF-->DOX). The second study, in patients with more than three involved nodes, compared four courses of full-dose DOX sequentially followed by eight courses of IV CMF (DOX-->CIVF) versus alternating two courses of the same CMF regimen with one course of DOX (CMF/DOX) for a total of 12 courses.Results After a median observation of 210 months, no statistically significant difference was documented in the first study (relapse-free survival hazard rate [HRI, 1.06; total survival HR, 1.03). In contrast, the delivery of DOX first, followed by CMF significantly reduced the risk of disease relapse (HR, 0.68; 95% Cl, 0.54 to 0.87; P =.0017) and death (HR, 0,74; 95% Cl, 0.57 to 0.95; P =.018) compared with the alternating regimen.Conclusion Anthracycline-containing regimens can further reduce the odds of relapse and death compared with CMF. However, the findings observed in our trials emphasize that the relative merits of anthracycline adjuvant programs also can depend on the modality of administration and must be assessed in properly designed trials in which the magnitude of the benefits can be weighed against potential risks.