Brain Etienne G C, Bachelot Thomas, Serin Daniel, Kirscher Sylvie, Graic Yvon, Eymard Jean-Christophe, Extra Jean-Marc, Combe Martin, Fourme Emmanuelle, Noguès Catherine, Rouëssé Jacques
Department of Medical Oncology, René Huguenin Cancer Centre, Saint-Cloud, France.
JAMA. 2005 May 18;293(19):2367-71. doi: 10.1001/jama.293.19.2367.
Adjuvant chemotherapy with new cytotoxic agents for breast cancer must be properly assessed for toxicity.
To describe adverse events associated with adjuvant chemotherapy for breast cancer, which led to premature termination of a clinical trial.
DESIGN, SETTING, AND PATIENTS: We conducted a prospective randomized multicenter study (Reposant sur des Arguments Pronostiques et Predictifs [RAPP]-01) to compare the effectiveness of 2 chemotherapy regimens. Patients (women aged 18-70 years) had primary unilateral breast cancer and either a moderate number of positive axillary lymph nodes (< or =3) or no positive axillary lymph nodes (N0), but were at a high risk of relapse. Patients were treated at 11 French cancer referral centers from June 1999 through January 2003. Primary prophylaxis for febrile neutropenia was not recommended in the study protocol.
Doxorubicin, 50 mg/m2, plus docetaxel, 75 mg/m2, or doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, given postoperatively for 4 courses.
The main end point was the disease-free survival rate at 5 years, as estimated using the Kaplan-Meier product limit method. Secondary end points included safety, which is the focus of this article, and overall survival.
A total of 627 women were enrolled. Median follow-up is currently too short (24 months) to analyze the primary end point. The trial was terminated prematurely when 2 deaths related to drug toxicity and 1 case of perforative peritonitis occurred among patients with febrile neutropenia, all in the doxorubicin-docetaxel group. The incidence of febrile neutropenia was significantly higher with the doxorubicin-docetaxel regimen (40.8%) than with the doxorubicin-cyclophosphamide regimen (7.1%) (P<.001).
A high risk of life-threatening complications associated with the doxorubicin-docetaxel regimen was found in this open-label controlled trial. The doxorubicin-docetaxel combination should not be considered as an alternative to the doxorubicin-cyclophosphamide regimen outside carefully designed studies that include primary prophylaxis for febrile neutropenia.
必须对用于乳腺癌的新型细胞毒性药物辅助化疗的毒性进行恰当评估。
描述与乳腺癌辅助化疗相关的不良事件，这些事件导致一项临床试验提前终止。
设计、地点和患者：我们开展了一项前瞻性随机多中心研究（基于预后和预测论据的储备研究[RAPP]-01），以比较两种化疗方案的疗效。患者（年龄在18至70岁的女性）患有原发性单侧乳腺癌，腋窝淋巴结阳性数量中等（≤3个）或腋窝淋巴结无阳性（N0），但复发风险高。患者于1999年6月至2003年1月在法国11个癌症转诊中心接受治疗。研究方案中不建议对发热性中性粒细胞减少进行一级预防。
术后给予多柔比星50mg/m²加多西他赛75mg/m²，或多柔比星60mg/m²加环磷酰胺600mg/m²，共4个疗程。
主要终点是采用Kaplan-Meier乘积限法估计的5年无病生存率。次要终点包括安全性（本文重点）和总生存率。
共纳入627名女性。目前中位随访时间过短（24个月），无法分析主要终点。当发热性中性粒细胞减少患者中发生2例与药物毒性相关的死亡和1例穿孔性腹膜炎时，试验提前终止；所有这些情况均发生在多柔比星-多西他赛组。多柔比星-多西他赛方案的发热性中性粒细胞减少发生率（40.8%）显著高于多柔比星-环磷酰胺方案（7.1%）（P<0.001）。
在这项开放标签对照试验中，发现多柔比星-多西他赛方案存在与危及生命的并发症相关的高风险。在未包括发热性中性粒细胞减少一级预防的精心设计的研究之外，多柔比星-多西他赛联合方案不应被视为多柔比星-环磷酰胺方案的替代方案。
Zotero 插件