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

Steven C. Brousell, Joseph J. Fantony, Megan G. Van Noord, Michael R. Harrison, Brant A. Inman

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

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 singleagent second-line, third-line, and maintenance therapy for advanced and metastatic UC. In firstline 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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalCore Evidence
Volume13
DOIs
StatePublished - Jan 24 2018
Externally publishedYes

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Transitional Cell Carcinoma
Safety
Carcinoma
Febrile Neutropenia
Survival
Neutropenia
Thrombocytopenia
Nausea
Therapeutics
Disease-Free Survival
Fatigue
Meta-Analysis
Anemia
Myalgia
Alopecia
Kaplan-Meier Estimate
Constipation
Standard of Care
vinflunine
Platinum

Keywords

  • Bladder cancer
  • Chemotherapy
  • Metastatic
  • Survival
  • Urothelial carcinoma
  • Vinflunine

ASJC Scopus subject areas

  • Reviews and References, Medical
  • Pharmacology

Cite this

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. / Brousell, Steven C.; Fantony, Joseph J.; Van Noord, Megan G.; Harrison, Michael R.; Inman, Brant A.

In: Core Evidence, Vol. 13, 24.01.2018, p. 1-12.

Research output: Contribution to journalReview article

@article{ab4d881257ed44cd8e5a721ee9171a27,
title = "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",
abstract = "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{\circledR}, Embase{\circledR}, 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 singleagent second-line, third-line, and maintenance therapy for advanced and metastatic UC. In firstline 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 = "Bladder cancer, Chemotherapy, Metastatic, Survival, Urothelial carcinoma, Vinflunine",
author = "Brousell, {Steven C.} and Fantony, {Joseph J.} and {Van Noord}, {Megan G.} and Harrison, {Michael R.} and Inman, {Brant A.}",
year = "2018",
month = "1",
day = "24",
doi = "10.2147/CE.S118670",
language = "English (US)",
volume = "13",
pages = "1--12",
journal = "Core Evidence",
issn = "1555-1741",
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T1 - Vinflunine for the treatment of advanced or metastatic transitional cell carcinoma of the urothelial tract

T2 - An evidence-based review of safety, efficacy, and place in therapy

AU - Brousell, Steven C.

AU - Fantony, Joseph J.

AU - Van Noord, Megan G.

AU - Harrison, Michael R.

AU - Inman, Brant A.

PY - 2018/1/24

Y1 - 2018/1/24

N2 - 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 singleagent second-line, third-line, and maintenance therapy for advanced and metastatic UC. In firstline 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.

AB - 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 singleagent second-line, third-line, and maintenance therapy for advanced and metastatic UC. In firstline 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.

KW - Bladder cancer

KW - Chemotherapy

KW - Metastatic

KW - Survival

KW - Urothelial carcinoma

KW - Vinflunine

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U2 - 10.2147/CE.S118670

DO - 10.2147/CE.S118670

M3 - Review article

AN - SCOPUS:85041130200

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SP - 1

EP - 12

JO - Core Evidence

JF - Core Evidence

SN - 1555-1741

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