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

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. Ob...

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Autores principales: Qu, Hong-Chen, Huang, Yan, Mu, Zhong-Yi, Lv, Hang, Xie, Qing-Peng, Wang, Kai, Hu, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974923/
https://www.ncbi.nlm.nih.gov/pubmed/32009946
http://dx.doi.org/10.3389/fphar.2019.01507
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author Qu, Hong-Chen
Huang, Yan
Mu, Zhong-Yi
Lv, Hang
Xie, Qing-Peng
Wang, Kai
Hu, Bin
author_facet Qu, Hong-Chen
Huang, Yan
Mu, Zhong-Yi
Lv, Hang
Xie, Qing-Peng
Wang, Kai
Hu, Bin
author_sort Qu, Hong-Chen
collection PubMed
description 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.
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spelling pubmed-69749232020-01-31 Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis Qu, Hong-Chen Huang, Yan Mu, Zhong-Yi Lv, Hang Xie, Qing-Peng Wang, Kai Hu, Bin Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2020-01-15 /pmc/articles/PMC6974923/ /pubmed/32009946 http://dx.doi.org/10.3389/fphar.2019.01507 Text en Copyright © 2020 Qu, Huang, Mu, Lv, Xie, Wang and Hu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Qu, Hong-Chen
Huang, Yan
Mu, Zhong-Yi
Lv, Hang
Xie, Qing-Peng
Wang, Kai
Hu, Bin
Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis
title Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis
title_full Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis
title_fullStr Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis
title_full_unstemmed Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis
title_short Efficacy and Safety of Chemotherapy Regimens in Advanced or Metastatic Bladder and Urothelial Carcinomas: An Updated Network Meta-Analysis
title_sort efficacy and safety of chemotherapy regimens in advanced or metastatic bladder and urothelial carcinomas: an updated network meta-analysis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974923/
https://www.ncbi.nlm.nih.gov/pubmed/32009946
http://dx.doi.org/10.3389/fphar.2019.01507
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