Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy
Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy
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DOI：
10.1158/1078-0432.ccr-05-0539
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发表时间：
2005-12-15
影响因子：
11.5
通讯作者：
Bonadonna, G
中科院分区：
文献类型：
--
作者：
Gianni, L;Baselga, J;Bonadonna, G
目的：欧洲可手术乳腺癌合作试验（ECTO）随机测试了辅助阿霉素随后静脉注射环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF;阿霉素-> 4CMF，A组）的疗效是否可以通过添加紫杉醇（阿霉素/紫杉醇-> CMF）作为辅助治疗（13组）或主要全身治疗（PST，C组）来改善。我们在这里报告的可行性，耐受性，局部抗肿瘤活性，和乳房protection rate.Methods：共1,355名妇女进入研究的可行性和安全性进行了比较，在A组与武器B加C。比较A组加B组与C组的手术结果。结果：所有组中国家癌症研究所3级或4级毒性均较低（< 5%）。神经病变在含紫杉醇组中更常见（2级，20.5% vs 5.0%; 3级，1.3% vs 0.2%）。在31个月随访时，所有组的无症状左心室射血分数下降相似，而A组3例患者（0.5%）和B + C组3例患者（0.3%）记录到症状性心脏毒性。PST诱导的临床完全加部分缓解率为78%，乳腺病理完全缓解率为23%，乳腺加腋窝病理完全缓解率为20%。在多变量分析中，只有雌激素受体（ER）状态与病理完全缓解显著相关（ER阴性的比值比，5.77; 95%可信区间，3.49-9.52; P < 0.0001）。PTS组腋窝分期明显下降（P < 0.001），保留乳房手术的可行性分别为65%和34%（P < 0.001）。作为PST，它明显活跃，允许乳房保留。大部分患者都接受了手术。
Purpose: The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin -> 4CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel -> CMF) as adjuvant (arm 13) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate.Methods: A total of 1,355 women entered the study Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C.Results: Grade 3 or 4 National Cancer Institute toxicities were low (< 5%) in all arms. Neuropathy was more frequent in the paclitaxel-containing arms (grade 2, 20.5% versus 5.0%; grade 3, 1.3% versus 0.2%). At 31 months of follow-up, asymptomatic drop of left ventricular ejection fraction was similar in all arms, whereas symptomatic cardiotoxicity was recorded in three patients (0.5%) in A and in three patients (0.3%) in B plus C. PST induced clinical complete plus partial remission in 78%, with an in-breast pathologic complete response rate of 23% and an in-breast plus axilla pathologic complete response rate of 20%. In the multivariate analysis, only estrogen receptor (ER) status was significantly associated with pathologic complete response (odds ratio for ER negative, 5.77; 95% confidence interval, 3.49-9.52; P < 0.0001). PTS induced a significant axillary downstaging (P < 0.001), and breast sparing surgery was feasible in 65% versus 34% (P < 0.001).Conclusions: Doxorubicin/paclitaxel -> CMF is feasible,safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing. surgery in a large fraction of patients.