Randomized, Double-Blind Trial of Carboplatin and Paclitaxel With Either Daily Oral Cediranib or Placebo in Advanced Non-Small-Cell Lung Cancer: NCIC Clinical Trials Group BR24 Study
Randomized, Double-Blind Trial of Carboplatin and Paclitaxel With Either Daily Oral Cediranib or Placebo in Advanced Non-Small-Cell Lung Cancer: NCIC Clinical Trials Group BR24 Study
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DOI：
10.1200/jco.2009.22.9427
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发表时间：
2010-01-01
影响因子：
45.3
通讯作者：
Seymour, Lesley
中科院分区：
文献类型：
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作者：
Goss, Glenwood D.;Arnold, Andrew;Seymour, Lesley
目的：本II/III期双盲研究评估了cediranib联合标准化疗作为晚期非小细胞肺癌（NSCLC）初始治疗的疗效和安全性。患者和方法：每3周给予杉醇（200 mg/m(2)）和卡铂（血清浓度-时间曲线下面积6），每日口服西地尼布或安慰剂30 mg（前45例患者接受45 mg）。无进展生存期（PFS）是II期中期分析的主要终点；如果PFS的风险比(HR) = 65岁，并且女性预测毒性增加，则进行III期。研究解除盲后10个月的生存更新（N = 296）支持cediranib优于安慰剂（中位数为10.5个月vs 10.1个月；HR, 0.78; 95% CI, 0.57 ~ 1.06; P = 0.11）。cediranib 30 mg组的死亡原因为NSCLC（81%）、方案毒性+/- NSCLC（13%）和其他（6%）；对于安慰剂组，他们分别是98%，0%和2%。结论在卡铂/紫杉醇的基础上加用西地尼可改善疗效和PFS，但在30mg剂量下出现不耐受。因此，加拿大国家癌症研究所临床试验组和澳大利亚肺癌试验组启动了一项随机、双盲、安慰剂对照试验，将cediranib 20mg与卡铂和紫杉醇联合用于晚期非小细胞肺癌。
PurposeThis phase II/III double-blind study assessed efficacy and safety of cediranib with standard chemotherapy as initial therapy for advanced non-small-cell lung cancer (NSCLC).Patients and MethodsPaclitaxel (200 mg/m(2)) and carboplatin (area under the serum concentration-time curve 6) were given every 3 weeks, with daily oral cediranib or placebo at 30 mg (first 45 patients received 45 mg). Progression-free survival (PFS) was the primary outcome of the phase II interim analysis; phase III would proceed if the hazard ratio (HR) for PFS = 65 years, and female sex predicted increased toxicity. Survival update (N = 296) 10 months after study unblinding favored cediranib over placebo (median of 10.5 months v 10.1 months; HR, 0.78; 95% CI, 0.57 to 1.06; P = .11). Causes of death in the cediranib 30-mg cohort were NSCLC (81%), protocol toxicity +/- NSCLC (13%), and other (6%); for the placebo group, they were 98%, 0%, and 2%, respectively.ConclusionThe addition of cediranib to carboplatin/paclitaxel results in improved response and PFS, but does not appear tolerable at a 30-mg dose. Consequently, the National Cancer Institute of Canada Clinical Trials Group and the Australasian Lung Cancer Trials Group initiated a randomized, double-blind, placebo-controlled trial of cediranib 20 mg with carboplatin and paclitaxel in advanced NSCLC.