Login Register Cart 0
Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

Author(s): Raafat Abdel-Malek, Kyrillus S. Shohdy*, Noha Abbas, Mohamed Ismail, Emad Hamada and Yasser Abdel-Kader

Volume 14, Issue 1, 2019

Page: [31 - 36] Pages: 6

DOI: 10.2174/1574886313666181001120752

Price: $65

Abstract

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy.

Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease.

Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy.

Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

Keywords: Vinflunine, urothelial cancer, safety, chemotherapy, second-line, TCCU.

« Previous Next »
Graphical Abstract

[1]
Bellmunt J, Wit R De, Vaughn DJ, et al. Pembrolizumab as Second-Line therapy for advanced urothelial carcinoma. N Engl J Med 2017; 376(11): 1015-26.
[2]
Powles T, Durán I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomised controlled trial. Lancet 2017; 6736(17): 1-11.
[3]
Faltas BM, Prandi D, Tagawa ST, et al. Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat Genet 2016 Dec 17; 48(12): 1490-9.
[4]
Gerullis H, Wawroschek F, Köhne C-H, Ecke TH. Vinflunine in the treatment of advanced urothelial cancer: Clinical evidence and experience. Ther Adv Urol 2017; 9(1): 28-35.
[5]
Siefker-Radtke AO, Necchi A, Park SH, et al. First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt). J Clin Oncol 2018; 36(15_suppl): 4503.
[6]
Culine S, Theodore C, De Santis M, et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer 2006; 94(10): 1395-401.
[7]
Bellmunt J, Theodore C, Demkov T, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009; 27(27): 4454-61.
[8]
Bellmunt J, Fougeray R, Rosenberg JE, et al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol 2013; 24(6): 1466-72.
[9]
Di Lorenzo G, Buonerba C, Bellelli T, et al. Third-Line Chemotherapy for metastatic urothelial cancer: A retrospective observational study. Medicine (Baltimore) 2015; 94(51): e2297.
[10]
Palacka P, Mego M, Obertova J, Chovanec M, Sycova-Mila Z, Mardiak J. The first Slovak experience with second-line vinflunine in advanced urothelial carcinomas. Klin Onkol 2014; 27(6): 429-33.
[11]
Hegele A, Goebell P, Matz U, Neuhaus T. Monotherapy with Intravenous vinflunine in patients with advanced or metastatic urothelial cancer after failure of a platinum-containing regimen: A retrospective analysis of german routine data. Urol Int 2014; 92(2): 174-9.
[12]
Brousell SC, Fantony JJ, Van Noord MG, Harrison MR, Inman BA. 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. Core Evid 2018; 13: 1-12.
[13]
Pond GR, Niegisch G, Rosenberg JE, et al. New 6-factor prognostic model for patients (pts) with advanced urothelial carcinoma (UC) receiving post-platinum atezolizumab. J Clin Oncol 2018; 36(6): 413.
[14]
García-Donas J, Font A, Pérez-Valderrama B, et al. Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): A multicentre, randomised, controlled, open. Lancet Oncol 2017; 18(5): 672-81.
[15]
De Santis M, Wiechno P, Bellmunt J, Lucas C, Su W, Albiges L. Vinflunine- gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: Results of an international randomized phase II trial (JASINT1). Ann Oncol 2016; 27: 449-54.
[16]
Gerullis H, Eimer C, Ecke TH, Georgas E, Arndt C, Otto T. Combined treatment with pazopanib and vinflunine in patients with advanced urothelial carcinoma refractory after first-line therapy. Anticancer Drugs 2013; 24(4): 422-5.
[17]
Pappot H, von der Maase H, Ullén A, Agerbæk M. Combined treatment with pemetrexed and vinflunine in patients with metastatic urothelial cell carcinoma after prior platinum-containing chemotherapy- results of an exploratory phase I study. Invest New Drugs 2018; 36(4): 615-8.
[18]
Sonpavde G, Pond GR, Choueiri TK, et al. Single-agent taxane versus taxane-containing combination chemotherapy as salvage therapy for advanced urothelial Carcinoma. Eur Urol 2016; 69(4): 634-41.
[19]
Vaughn DJ, Srinivas S, Stadler WM, et al. Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: Results of a large phase 2 study. Cancer 2009; 115(18): 4110-7.
[20]
Schinzari G, Rossi E, Pierconti F, et al. Monoinstitutional real world experience in management of Vinflunine as second line therapy for transitional cell carcinoma of the urothelium. Oncotarget 2018; 9(9): 8765-71.
[21]
McCaffrey JA, Hilton S, Mazumdar M, et al. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol 1997; 15(5): 1853-7.
[22]
Kim YS, Lee S, Park SH, et al. A Phase II study of weekly docetaxel as second-line chemotherapy in patients with metastatic urothelial carcinoma. Clin Genitourin Cancer 2016; 14(1): 76-81.
[23]
Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol 2002; 20(4): 937-40.
[24]
Akaza H, Naito S, Usami M, Miki T, Miyanaga N, Taniai H. Efficacy and safety of gemcitabine monotherapy in patients with transitional cell carcinoma after cisplatin-containing therapy: A Japanese experience. Jpn J Clin Oncol 2007; 37(3): 201-6.
[25]
Kruczynski A, Hill BT. Vinflunine, the latest Vinca alkaloid in clinical development. A review of its preclinical anticancer properties. Crit Rev Oncol Hematol 2001; 40(2): 159-73.
[26]
Guglieri-López B, Pérez-Pitarch A, Porta-Oltra B, Ferriols-Lisart F, Climente-Martí M, Alós-Almiñana M. Effectiveness, toxicity, and economic evaluation of vinflunine for the treatment of patients with transitional cell carcinoma in the Spanish outpatient setting. Anticancer Drugs 2015; 26(8): 860-5.
[27]
Sarfaty M, Hall PS, Chan KKW, et al. Cost-effectiveness of pembrolizumab in second-line advanced bladder cancer. Eur Urol 2018; 74(1): 57-62.
[28]
Castellano D, Puente J, de Velasco G, et al. Safety and effectiveness of vinflunine in patients with metastatic transitional cell carcinoma of the urothelial tract after failure of one platinum-based systemic therapy in clinical practice. BMC Cancer 2014; 14(1): 779.
[29]
Pistamaltzian N, Tzannis K, Pissanidou V, et al. Treatment of relapsed urothelial bladder cancer with vinflunine. Anticancer Drugs 2016; 27(1): 48-53.

Rights & Permissions Print Cite
Article Metrics
57
3
1
1
© 2024 Bentham Science Publishers | Privacy Policy