Qu Hong-Chen, Huang Yan, Mu Zhong-Yi, Lv Hang, Xie Qing-Peng, Wang Kai, Hu Bin
Department of Urological Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute, Shenyang, China.
Front Pharmacol. 2020 Jan 15;10:1507. doi: 10.3389/fphar.2019.01507. eCollection 2019.
Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) have been the first-line treatments for advanced or metastatic urothelial carcinoma (AMUC). However, their effects are unsatisfactory, and more drugs and regimens still need to be explored. We aimed to comprehensively compare all possible regimens with GC or MVAC in randomized controlled trials (RCTs) by network meta-analysis. We searched the PubMed, Embase, and Cochrane databases for RCTs that evaluated regimens compared to GC or MVAC on AMUC patients. The major outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). A network meta-analysis was used to assess the effectiveness and safety of the included treatment regimens, and the regimens were then clustered by the average linkage method. A total of 19 trials that assessed 3,363 AMUC patients were included. For PFS, paclitaxel plus GC (PGC) was significantly superior to GC (log hazard ratio (HR): -0.16; 95% confidence interval (CI): -0.32, 0.00) with a moderate level of reliability. However, there was no significant difference between PGC and MVAC (log HR: -0.03; 95% CI: -0.27, 0.20). For OS, PGC was significantly superior to GC (log HR:-0.17; 95% CI: -0.33, -0.00) with a moderate reliability level but not significantly different from MVAC (log HR: -0.10; 95% CI: -0.35, 0.15). Analysis of ORR showed that PGC was superior to MVAC (log odds ratio (OR): 0.59; 95% CI: 0.02, 1.16) with a low reliability level and GC (log OR: 0.41; 95% CI: 0.12, 0.71) with a moderate reliability level. In the cluster results, PGC and sorafenib plus GC (GCS) exhibited relative advantages in efficiency, followed by MVAC and apatorsen plus GC (GCA); however, PGC, gemcitabine plus carboplatin (GP), and MVAC had more serious side effects. In our analysis, PGC was superior to MVAC and GC in only the ORR results and superior to GC in the OS and PFS results but was not significantly different from MVAC. More individualized therapies with targeted drugs need to be studied.
吉西他滨联合顺铂（GC）以及甲氨蝶呤、长春花碱、阿霉素和顺铂（MVAC）一直是晚期或转移性尿路上皮癌（AMUC）的一线治疗方案。然而，它们的疗效并不理想，仍需探索更多的药物和治疗方案。我们旨在通过网络荟萃分析，在随机对照试验（RCT）中全面比较所有可能与GC或MVAC联合使用的治疗方案。我们在PubMed、Embase和Cochrane数据库中检索了评估与GC或MVAC相比用于AMUC患者治疗方案的RCT。主要结局指标为无进展生存期（PFS）、总生存期（OS）和客观缓解率（ORR）。采用网络荟萃分析评估纳入治疗方案的有效性和安全性，然后通过平均连锁法对这些方案进行聚类。共纳入了19项评估3363例AMUC患者的试验。对于PFS，紫杉醇联合GC（PGC）显著优于GC（对数风险比（HR）：-0.16；95%置信区间（CI）：-0.32，0.00），可靠性为中等水平。然而，PGC与MVAC之间无显著差异（对数HR：-0.03；95%CI：-0.27，0.20）。对于OS，PGC显著优于GC（对数HR：-0.17；95%CI：-0.33，-0.00），可靠性为中等水平，但与MVAC无显著差异（对数HR：-0.10；95%CI：-0.35，0.15）。ORR分析显示，PGC优于MVAC（对数优势比（OR）：0.59；95%CI：0.02，1.16），可靠性较低，且优于GC（对数OR：0.41；95%CI：0.12，0.71），可靠性为中等水平。在聚类结果中，PGC和索拉非尼联合GC（GCS）在疗效方面表现出相对优势，其次是MVAC和阿帕托森联合GC（GCA）；然而，PGC、吉西他滨联合卡铂（GP）和MVAC有更严重的副作用。在我们的分析中，PGC仅在ORR结果上优于MVAC和GC，在OS和PFS结果上优于GC，但与MVAC无显著差异。需要研究更多使用靶向药物的个体化治疗方案。
