The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
The NCIC Clinical Trials Group, Kingston, Ontario, Canada; The Australasian Lung Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
Eur J Cancer. 2014 Mar;50(4):706-12. doi: 10.1016/j.ejca.2013.11.032. Epub 2013 Dec 17.
This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer.
Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70.
The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia.
The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.
本随机、双盲、安慰剂对照研究评估了血管内皮生长因子受体 1-3 抑制剂西地尼布（cediranib）联合标准卡铂/紫杉醇化疗治疗晚期非小细胞肺癌的疗效。
符合条件的患者接受紫杉醇（200mg/m²）和卡铂（浓度时间曲线下面积 6）静脉输注，每 3 周一次。在第 1 周期的第 1 天开始每天口服西地尼布/安慰剂 20mg，并在完成 4-6 周期化疗后继续单药治疗。研究的主要终点为总生存期（OS）。如果首次入组的 260 例患者中前 170 例出现进展或死亡时的无进展生存（PFS）的中期分析（IA）显示 PFS 的风险比（HR）为≤0.70，则试验将继续全额入组。
在 IA 时，由于无效而停止了试验（PFS 的 HR 为 0.89，95%置信区间 [CI] 0.66-1.20，p=0.45）。对所有 306 例入组患者进行了最终分析。西地尼布的添加增加了缓解率（[RR]52%比 34%，p=0.001），但并未显著改善 PFS（HR 0.91，95%CI 0.71-1.18，p=0.49）或 OS（HR 0.94，95%CI 0.69-1.30，p=0.72）。西地尼布组患者更常见 3 级高血压、腹泻和厌食。
每日 20mg 西地尼布联合卡铂/紫杉醇化疗可提高 RR 和毒性，但不能提高生存率。
