PMID- 34749886 OWN - NLM STAT- MEDLINE DCOM- 20220429 LR - 20220429 IS - 1532-8708 (Electronic) IS - 0093-7754 (Linking) VI - 48 IP - 3 DP - 2021 Jun TI - Adverse events of different chemotherapy regimens in the first-line treatment of patients with advanced or metastatic urothelial cancer: A systematic review and network meta-analysis of randomized controlled trials. PG - 181-192 LID - S0093-7754(21)00057-9 [pii] LID - 10.1053/j.seminoncol.2021.09.005 [doi] AB - INTRODUCTION: The present systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to compare the mortality rates related to adverse events (AEs) and discontinuation of treatment due to toxicity as well as all AEs of currently used chemotherapy regimens for first-line therapy of advanced or metastatic urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The MEDLINE and EMBASE databases were searched for articles published between January 2000 and June 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis extension statement for NMA. Eligible studies included RCTs comparing different first-line chemotherapy regimens for treating advanced or metastatic UCB and AEs as outcome measures. A NMA was performed to assess the mortality rates related to AEs and discontinuation of treatment due to toxicity as well as all AEs. RESULTS: Fourteen trials comprising 2,615 patients met our eligibility criteria and formal NMAs were conducted. Results revealed that gemcitabine plus carboplatin had the lowest likelihood of mortality related to AEs (P score: 0.8079), while larotaxel plus cisplatin and paclitaxel, cisplatin plus gemcitabine had both a lower toxicity rate leading to discontinuation (P score: 0.7295 and P score: 0.7242, respectively). Compared with gemcitabine plus cisplatin (GC), most chemotherapy regimens were associated with a lower likelihood of thrombocytopenia, anemia, and cardiovascular toxicity. In contrast, most chemotherapy regimens compared with GC were associated with a higher likelihood of neutropenia, central (fatigue, neuropathy) and gastrointestinal AEs, infections, as well as renal and pulmonary toxicities. CONCLUSION: Results of the present study demonstrated that hematological toxicity was the most prevalent AE associated with gemcitabine-containing regimens, while central AEs and febrile neutropenia were more commonly in taxane-containing regimens. GC had the lowest rate of gastrointestinal AEs, infection disorders, and pulmonary toxicities. Cisplatin-containing regimens were associated with a higher rate of renal and cardiovascular toxicity. These differential AEs may help in the detection of the personalized therapy in addition of efficacy data. CI - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Laukhtina, Ekaterina AU - Laukhtina E AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. FAU - Mori, Keiichiro AU - Mori K AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. FAU - Mostafaei, Hadi AU - Mostafaei H AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Merseburger, Axel S AU - Merseburger AS AD - Department of Urology, Campus Lubeck, University Hospital Schleswig-Holstein, Lubeck, Germany. FAU - Nyirady, Peter AU - Nyirady P AD - Department of Urology, Semmelweis University, Budapest, Hungary. FAU - Moschini, Marco AU - Moschini M AD - Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland; Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele. FAU - Quhal, Fahad AU - Quhal F AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. FAU - Pradere, Benjamin AU - Pradere B AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. FAU - Motlagh, Reza Sari AU - Motlagh RS AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Enikeev, Dmitry AU - Enikeev D AD - Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. FAU - Shariat, Shahrokh F AU - Shariat SF AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, New York, USA; Department of Urology, University of Texas Southwestern, Dallas, Texas, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan. Electronic address: shahrokh.shariat@meduniwien.ac.at. CN - European Association of Urology-Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU) LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20211002 PL - United States TA - Semin Oncol JT - Seminars in oncology JID - 0420432 RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - *Carcinoma, Transitional Cell/drug therapy MH - Cisplatin/adverse effects MH - Female MH - Humans MH - Male MH - Network Meta-Analysis MH - Randomized Controlled Trials as Topic MH - *Urinary Bladder Neoplasms/drug therapy OTO - NOTNLM OT - Adverse events OT - Chemotherapy OT - First-line OT - Network meta-analyses OT - RCT OT - UCB OT - Urothelial cancer COIS- Acknowledgments Ekaterina Laukhtina is supported by the EUSP Scholarship of the European Association of Urology (EAU). EDAT- 2021/11/10 06:00 MHDA- 2022/04/30 06:00 CRDT- 2021/11/09 05:47 PHST- 2020/09/19 00:00 [received] PHST- 2021/09/01 00:00 [revised] PHST- 2021/09/15 00:00 [accepted] PHST- 2021/11/09 05:47 [entrez] PHST- 2021/11/10 06:00 [pubmed] PHST- 2022/04/30 06:00 [medline] AID - S0093-7754(21)00057-9 [pii] AID - 10.1053/j.seminoncol.2021.09.005 [doi] PST - ppublish SO - Semin Oncol. 2021 Jun;48(3):181-192. doi: 10.1053/j.seminoncol.2021.09.005. Epub 2021 Oct 2.