Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer.
Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer.
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每周一次，每3周的紫杉醇和卡泊素卵巢癌。
DOI：
10.1056/nejmoa1505067
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发表时间：
2016-02-25
期刊：
影响因子：
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通讯作者：
Monk BJ
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作者：
Chan JK;Brady MF;Penson RT;Huang H;Birrer MJ;Walker JL;DiSilvestro PA;Rubin SC;Martin LP;Davidson SA;Huh WK;O'Malley DM;Boente MP;Michael H;Monk BJ
每周剂量密集的紫杉醇(导致更高的给药频率)加卡铂每3周一次，或在紫杉醇和卡铂的基础上每3周加用贝伐单抗，已显示出对卵巢癌的疗效。我们建议在接受贝伐单抗和未接受贝伐单抗的患者中，与每3周给予一次紫杉醇和卡铂相比，每周剂量密集的紫杉醇和卡铂是否会延长无进展生存期。我们根据患者是否选择接受贝伐单抗进行前瞻性分层，然后随机分配给他们接受紫杉醇和卡铂(剂量相当于曲线下面积[AUC]为6)，每3周每平方米175毫克静脉注射，共6个周期，或紫杉醇，每周80毫克每平方米，加卡铂(AUC，6)，共6个周期。主要终点是无进展生存。共有692名患者入选，其中84%的患者选择接受贝伐单抗治疗。在意向治疗分析中，每周一次的紫杉醇与每3周一次的无进展生存期没有关联(分别为14.7个月和14.0个月；疾病进展或死亡的风险比，0.89；95%可信区间[CI]，0.74至1.06；P=0.18)。在没有接受贝伐单抗治疗的患者中，每周接受紫杉醇治疗的无进展生存期比每3周接受一次紫杉醇治疗的患者多3.9个月(14.2个月比10.3个月；风险比0.62；95%CI，0.40到0.95；P=0.03)。然而，在接受贝伐单抗治疗的患者中，每周一次的紫杉醇与每三周一次的紫杉醇相比并没有显著延长无进展生存期(分别为14.9个月和14.7个月；风险比，0.99；95%CI，0.83至1.20；P=0.60)。评估治疗效果同质性的交互作用测试显示，贝伐单抗治疗和不使用贝伐单抗治疗之间有显著差异(P=0.047)。每周接受紫杉醇治疗的患者的3级或4级贫血率高于每3周接受一次紫杉醇治疗的患者(36%比16%)，以及更高的2级到4级感觉神经病变的发生率(26%比18%)；然而，他们的3级或4级中性粒细胞减少症的发生率(72%比83%)较低。总体而言，每周一次的紫杉醇与每三周一次的紫杉醇相比，并没有延长卵巢癌患者的无进展生存期。(由国家癌症研究所和基因技术公司资助；GOG-0262 ClinicalTrials.gov编号，NCT01167712。)
A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P = 0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P = 0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P = 0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P = 0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.)