title: Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.
abstract: BACKGROUND
  Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients.
  
  
  METHODS
  Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0).
  
  
  RESULTS
  Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups.
  
  
  CONCLUSIONS
  In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective trials due to its potential survival benefit in advanced UC patients.
authors.affiliation: Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhi
authors.affiliation: Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.affiliation: Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Zhou
authors.affiliation: Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Zhan-Song
authors.initials: ZS
authors.lastname: Zhou
keywords: advanced urothelial cancer; cytotoxic agents; efficacy; meta-analysis; salvage chemotherapy