Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis

Abstract

Background: 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. Objective: We aimed to comprehensively compare all possible regimens with GC or MVAC in randomized controlled trials (RCTs) by network meta-analysis. Methods: 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. Results: 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. Conclusions: 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.

Angiogenesis Driven by the CEBPD–hsa-miR-429–VEGFA Signaling Axis Promotes Urothelial Carcinoma Progression

“…Administration of gemcitabine plus cisplatin is now considered as a first-line chemotherapy regimen for advanced or metastatic UC [ 31 ], but the prognostic outcome is still unsatisfactory, and the demand for combined remedy is pressing. Metastasis progression and nourishment supply strongly rely on vascularization in tumors [ 32 ].…”

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective

“…Chemotherapy regimens for BC are largely cisplatin-based. Further, gemcitabine plus cisplatin is a preferred chemotherapy regimen compared to MVAC (methotrexate, vinblastine sulfate, doxorubicin hydrochloride (Adriamycin), and cisplatin) due to its better tolerability in the neoadjuvant and adjuvant/salvage settings [ 51 , 53 , 54 , 55 , 56 , 57 , 58 ]. Despite chemotherapy, the median survival of patients with metastatic disease is less than two years due to treatment failure.…”

Clinical and economic effectiveness of using immunotherapeutic drugs in patients with urothelial carcinoma in the healthcare system of the Russian Federation

“…Использование ХТ на основе цисплатина связано с высокой токсичностью у пациентов с УР, особенно при наличии сопутствующих заболеваний, снижающих способность переносить агрессивную терапию [9]. Таким образом, число кандидатов на ХТ в режиме GC (гемцитабин, цисплатин) оказывается ограниченным.…”