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.

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).

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.

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.

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.

Seminars in oncology. 2021 Oct 02 [Epub]

Ekaterina Laukhtina, Keiichiro Mori, Hadi Mostafaei, Axel S Merseburger, Peter Nyirady, Marco Moschini, Fahad Quhal, Benjamin Pradere, Reza Sari Motlagh, Dmitry Enikeev, Shahrokh F Shariat, European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU)

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, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., 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., Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany., Department of Urology, Semmelweis University, Budapest, Hungary., Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland; Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., 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., Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., 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: .

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