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Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis

Authors Wu X, Zhi Y, He P, Zhou X, Zheng J, Chen Z, Zhou Z

Received 24 September 2015

Accepted for publication 6 November 2015

Published 15 March 2016 Volume 2016:9 Pages 1535—1543


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 3

Editor who approved publication: Professor Daniele Santini

Xiao-Jun Wu, Yi Zhi, Peng He, Xiao-Zhou Zhou, Ji Zheng, Zhi-Wen Chen, Zhan-Song Zhou

Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China

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.
Conclusion: 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.

Keywords: advanced urothelial cancer, salvage chemotherapy, cytotoxic agents, meta-analysis, efficacy

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