Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China.
Lung. 2011 Dec;189(6):437-43. doi: 10.1007/s00408-011-9332-1. Epub 2011 Oct 11.
The purpose of this study was to assess the efficacy and toxicity of vandetanib in the second-line treatment for advanced non-small cell lung cancer (NSCLC).
We systematically searched for randomized clinical trials that compared therapy with vandetanib versus standard second-line treatment, including docetaxel, pemetrexed, erlotinib, or gefitinib, as second-line treatment for patients with histologically proven non-small-cell lung cancer. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, overall response rate, and grade 3 or 4 toxicity. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, TX, USA).
Four randomized clinical trials (N = 3,292 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (hazards ration (HR), 0.91; 95% confidence interval (CI), 0.83-1.00; P = 0.039) and overall response rate (relative risk (RR), 1.49; 95% CI, 1.04-2.14; P = 0.03) in therapy with vandetanib group compared with standard second-line therapy group, although the pooled HR for overall survival (HR, 0.95; 95% CI, 0.88-1.03; P = 0.191) showed no significant difference between the two groups. In addition, there were less incidences of grade 3 or 4 anemia (RR, 0.39; 95% CI, 0.22-0.67; P = 0.001) in therapy with vandetanib group. With regard to the risk of grade 3 or 4 neutropenia (RR, 1.19; 95% CI, 1.0-1.43; P = 0.054), diarrhea (RR, 1.38; 95% CI, 1.0-1.94; P = 0.059), nausea and vomiting (RR, 0.77; 95% CI, 0.48-1.26; P = 0.308), rash (RR, 2.83; 95% CI, 0.73-10.9; P = 0.131), cough (RR, 1.19; 95% CI, 1.0-1.43; P = 0.054), and fatigue (RR, 1.0; 95% CI, 0.747-1.35; P = 0.971), there was no significant difference between the two groups.
Therapy with vandetanib offered a clinically meaningful and statistically significant improvement in PFS and ORR in patients with advanced NSCLC but did not benefit overall survival. Therapy with vandetanib regimens might be suggested as second-line treatment for advanced NSCLC based on a similar toxicity profile compared with standard second-line therapy.
本研究旨在评估凡德他尼在晚期非小细胞肺癌（NSCLC）二线治疗中的疗效和毒性。
我们系统地检索了比较凡德他尼与多西他赛、培美曲塞、厄洛替尼或吉非替尼等标准二线治疗作为组织学证实的非小细胞肺癌患者二线治疗的随机临床试验。主要终点是总生存期（OS）。次要终点是无进展生存期、总缓解率和 3 或 4 级毒性。两名独立评审员从研究中提取数据。使用 Stata 版本 10.0 软件（Stata Corporation，College Station，TX，USA）进行荟萃分析。
四项随机临床试验（N=3292 例患者）符合条件。荟萃分析显示，凡德他尼组的无进展生存期（风险比（HR），0.91；95%置信区间（CI），0.83-1.00；P=0.039）和总缓解率（相对风险（RR），1.49；95%CI，1.04-2.14；P=0.03）有显著改善，但两组总生存期的汇总 HR（HR，0.95；95%CI，0.88-1.03；P=0.191）无显著差异。此外，凡德他尼组 3 或 4 级贫血的发生率较低（RR，0.39；95%CI，0.22-0.67；P=0.001）。至于 3 或 4 级中性粒细胞减少症（RR，1.19；95%CI，1.0-1.43；P=0.054）、腹泻（RR，1.38；95%CI，1.0-1.94；P=0.059）、恶心和呕吐（RR，0.77；95%CI，0.48-1.26；P=0.308）、皮疹（RR，2.83；95%CI，0.73-10.9；P=0.131）、咳嗽（RR，1.19；95%CI，1.0-1.43；P=0.054）和疲劳（RR，1.0；95%CI，0.747-1.35；P=0.971）的风险，两组间无显著差异。
凡德他尼治疗可显著改善晚期 NSCLC 患者的无进展生存期和总缓解率，但对总生存期无获益。基于与标准二线治疗相似的毒性谱，凡德他尼方案可作为晚期 NSCLC 的二线治疗选择。
