Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Cancer. 2012 Mar;48(4):527-37. doi: 10.1016/j.ejca.2011.12.022. Epub 2012 Jan 28.
Cediranib is a highly potent vascular endothelial growth factor (VEGF) signalling inhibitor with activity against VEGF receptors 1, 2 and 3. This Phase II, randomised, double-blind, parallel-group study compared the efficacy of cediranib with placebo in patients with metastatic or recurrent clear cell renal cell carcinoma who had not previously received a VEGF signalling inhibitor.
Patients were randomised (3:1) to cediranib 45 mg/day or placebo. The primary objective was comparison of change from baseline in tumour size after 12 weeks of therapy. Secondary objectives included response rate and duration, progression-free survival (PFS) and safety and tolerability. Patients in the placebo group could cross over to open-label cediranib at 12 weeks or earlier if their disease had progressed. This study has been completed and is registered with ClinicalTrials.gov, number NCT00423332.
Patients (n=71) were randomised to receive cediranib (n=53) or placebo (n=18). The primary study outcome revealed that, after 12weeks of therapy, there was a significant difference in mean percentage change from baseline in tumour size between the cediranib (-20%) and placebo (+20%) arms (p<0.0001). Eighteen patients (34%) on cediranib achieved a partial response and 25 (47%) experienced stable disease. Cediranib treatment prolonged PFS significantly compared with placebo (hazard ratio (HR)=0.45, 90%confidence interval: 0.26-0.76, p=0.017; median PFS 12.1 versus 2.8 months). The most common adverse events in patients receiving cediranib were diarrhoea (74%), hypertension (64%), fatigue (58%) and dysphonia (58%).
Cediranib monotherapy demonstrated significant evidence of antitumour activity in patients with advanced renal cell carcinoma. The adverse event profile was consistent with previous studies of cediranib 45 mg.
西地尼布是一种强效的血管内皮生长因子（VEGF）信号抑制剂，对 VEGF 受体 1、2 和 3 均有活性。这项 II 期、随机、双盲、平行组研究比较了西地尼布与安慰剂在既往未接受过 VEGF 信号抑制剂治疗的转移性或复发性透明细胞肾细胞癌患者中的疗效。
患者按 3:1 随机分配至西地尼布 45mg/天或安慰剂组。主要研究终点为治疗 12 周后肿瘤大小相对于基线的变化。次要研究终点包括缓解率和缓解持续时间、无进展生存期（PFS）以及安全性和耐受性。安慰剂组的患者如果疾病进展，可在 12 周或更早时交叉至开放标签西地尼布治疗。本研究已完成，在 ClinicalTrials.gov 注册，编号为 NCT00423332。
71 例患者被随机分配至西地尼布组（n=53）或安慰剂组（n=18）。主要研究终点显示，治疗 12 周后，西地尼布组（-20%）和安慰剂组（+20%）的肿瘤大小相对于基线的平均百分比变化有显著差异（p<0.0001）。18 例（34%）西地尼布治疗患者达到部分缓解，25 例（47%）患者疾病稳定。与安慰剂相比，西地尼布治疗显著延长了 PFS（风险比（HR）=0.45，90%置信区间：0.26-0.76，p=0.017；中位 PFS 12.1 个月对 2.8 个月）。接受西地尼布治疗的患者最常见的不良反应是腹泻（74%）、高血压（64%）、疲劳（58%）和发音困难（58%）。
西地尼布单药治疗在晚期肾细胞癌患者中显示出显著的抗肿瘤活性。不良事件谱与之前西地尼布 45mg 的研究一致。
