Vinflunine for the treatment of advanced or metastatic transitional cell carcinoma of the urothelial tract: an evidence-based review of safety, efficacy, and place in therapy
Received 1 August 2017
Accepted for publication 1 November 2017
Published 24 January 2018 Volume 2018:13 Pages 1—12
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Garry Walsh
Steven C Brousell,1 Joseph J Fantony,1 Megan G Van Noord,2 Michael R Harrison,3 Brant A Inman1
1Division of Urology, 2Division of Research and Education Services, 3Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA
Background: A systematic review and meta-analysis of the use of systemic vinflunine (VIN) in the treatment of urothelial carcinoma (UC) was performed to evaluate its efficacy based on current available clinical data.
Methods: This review was prospectively registered at the International Prospective Register of Systematic Reviews, PROSPERO (registration CRD42016049294). Electronic databases including MEDLINE®, Embase®, Cochrane Central Register of Controlled Trials, and Web of Science were searched through December 2016. We performed a meta-analysis of the published data. Primary end points were progression-free survival (PFS) and overall survival (OS). Numerous secondary clinical outcomes were analyzed including response and toxicity data.
Results: We identified 382 publications, of which 35 met inclusion criteria for this review representing 29 unique studies. A total of 2,255 patients received VIN for the treatment of UC in the included studies. OS and PFS were analyzed in a pooled Kaplan–Meier analysis. Response data were available for 1,416 VIN-treated patients with random effects proportion of complete response in 1%, partial response in 18%, and overall response rate of 21%. Toxicity analysis revealed fatigue (40.1%), nausea (33.9%), constipation (34.1%), and alopecia (26.0%) as the most prevalent overall non-hematologic adverse events (AEs). Most prevalent grade 3–4 AEs were fatigue (10.2%), abdominal pain (8.2%), myalgias (2.5%), and nausea (2.3%). Most common hematologic AEs of all grades were anemia (56.6%), neutropenia (46.0%), thrombocytopenia (25.5%), and febrile neutropenia (6.6%). Grade 3–4 hematologic AEs had the following pooled rates: neutropenia, 24.6%; anemia, 10.2%; febrile neutropenia, 5.4%; and thrombocytopenia, 3.0%.
Conclusion: VIN has been explored as a combination first-line treatment as well as a single-agent second-line, third-line, and maintenance therapy for advanced and metastatic UC. In first-line treatment of UC, either as a maintenance agent after cisplatin or as a primary combination therapy, VIN may be a promising alternative to current treatments. Further studies are needed to compare first-line combination VIN regimens to the current standard of care in order to assess long-term survival outcomes. Second- and third-line VIN monotherapy does provide a proven, although limited, survival benefit in platinum-refractory patients.
Keywords: vinflunine, urothelial carcinoma, bladder cancer, metastatic, survival, chemotherapy
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