Phase III Trial Evaluating the Addition of Paclitaxel to Doxorubicin Followed by Cyclophosphamide, Methotrexate, and Fluorouracil, As Adjuvant or Primary Systemic Therapy: European Cooperative Trial in Operable Breast Cancer
Phase III Trial Evaluating the Addition of Paclitaxel to Doxorubicin Followed by Cyclophosphamide, Methotrexate, and Fluorouracil, As Adjuvant or Primary Systemic Therapy: European Cooperative Trial in Operable Breast Cancer
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DOI：
10.1200/jco.2008.19.2567
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发表时间：
2009-05-20
影响因子：
45.3
通讯作者：
Bonadonna, Gianni
中科院分区：
文献类型：
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作者：
Gianni, Luca;Baselga, Jose;Bonadonna, Gianni
1,355例可手术乳腺癌患者随机分为三组：手术+阿霉素(75 mg/m(2))+环磷酰胺、甲氨蝶呤、氟尿嘧啶(CMF；ARM A)；手术+紫杉醇(200 mg/m(2))+阿霉素(60 mg/m(2))；或紫杉醇(200 mg/m(2))加阿霉素(60 mg/m(2))，然后进行CMF和手术(组C)。两个主要目的是评价术后化疗加紫杉醇(B组对A组)和初次化疗与辅助化疗(B组对C组)对无复发生存(RFS)的影响。结果阿霉素加紫杉醇加CMF作为辅助化疗或作为一次化疗耐受性良好。与单用阿霉素后辅佐CMF相比，辅助剂阿霉素加紫杉醇后CMF可显著改善RFS(危险比[HR]，0.73；P=0.03)。远距离RFS也有类似的改善(HR，0.70；P=0.027)。术前给予紫杉醇/阿霉素/CMF方案与术后给予相同方案相比，RFS差异无统计学意义(HR，1.21；P=0.18)。然而，术前化疗的保乳术率显著高于术前化疗(63%比34%；P<；.001)。结论在以蒽环类药物为基础的辅助治疗中加入紫杉醇可显著改善RFS和远程RFS。当给予主要的系统治疗时，含有紫杉醇的方案允许相当大比例的患者进行保乳手术。
PurposeTo evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy.Patients and MethodsA total of 1,355 women with operable breast cancer were randomly assigned to one of three treatments: surgery followed by adjuvant doxorubicin (75 mg/m(2)) followed by cyclophosphamide, methotrexate, and fluorouracil (CMF; arm A); surgery followed by adjuvant paclitaxel (200 mg/m(2)) plus doxorubicin (60 mg/m(2)), followed by CMF (arm B); or paclitaxel (200 mg/m(2)) plus doxorubicin (60 mg/m(2)) followed by CMF followed by surgery (arm C). The two coprimary objectives were to assess the effects on relapse-free survival (RFS) of the addition of paclitaxel to postoperative chemotherapy (arm B v arm A) and primary chemotherapy versus adjuvant chemotherapy (arm B v arm C).ResultsDoxorubicin plus paclitaxel followed by CMF was well-tolerated as adjuvant or as primary chemotherapy. The addition of paclitaxel to adjuvant doxorubicin followed by CMF significantly improved RFS compared with adjuvant doxorubicin alone followed by CMF (hazard ratio [HR], 0.73; P = .03). Distant RFS was similarly improved (HR, 0.70; P = .027). There was no significant difference in RFS when the paclitaxel/doxorubicin/CMF chemotherapy was given before surgery compared with the same regimen given after surgery (HR, 1.21; P = .18). However, the rate of breast-conserving surgery was significantly higher with preoperative chemotherapy (63% v 34%; P < .001).ConclusionIncorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significant improvement in RFS and distant RFS. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients.