Originally published as JCO Early Release 10.1200/JCO.2008.20.5534 on August 17 2009

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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

From the Vall d'Hebron University Hospital; University Hospital del Mar-IMIM, Barcelona, Spain; Hopital Foch, Suresnes; Centre Oscar Lambret, Lille; Institut de Recherche Pierre Fabre, Boulogne; Hôpital Henri Mondor, Créteil, France; Marie Curie Institute, Warsaw; SPZ Pulmonologii Oddzial Onkologii, Olsztyn, Poland; City Polyprofile Hospital N2, Saint Petersburg; Medical Radiological Research Center, Kaluga Region, Russian Federation; Herlev University Hospital, Herlev; Rigshospitalet, Copenhagen, Denmark; and Department of Oncology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada.

Corresponding author: Joaquim Bellmunt, MD, Department of Medical Oncology, University Hospital Del Mar, Passeig Marítim 25-29, E-08003 Barcelona, Spain; e-mail: jbellmunt{at}imas.imim.es.

Purpose Vinflunine (VFL) is a new microtubule inhibitor that has activity against transitional cell carcinoma of urothelial tract (TCCU). We conducted a randomized phase III study of VFL and best supportive care (BSC) versus BSC alone in the treatment of patients with advanced TCCU who had experienced progression after a first-line platinum-containing regimen.

Patients and Methods The study was designed to compare overall survival (OS) between patients receiving VFL + BSC (performance status [PS] = 0: 320 mg/m², every 3 weeks; PS = 0 with previous pelvic radiation and PS = 1: 280 mg/m² subsequently escalated to 320 mg/m²) or BSC.

Results Three hundred seventy patients were randomly assigned (VFL + BSC, n =253; BSC, n = 117). Both arms were well balanced except there were more patients with PS more than 1 (10% difference) in the BSC arm. Main grade 3 or 4 toxicities for VFL + BSC were neutropenia (50%), febrile neutropenia (6%), anemia (19%), fatigue (19%), and constipation (16%). In the intent-to-treat population, the objective of a median 2-month survival advantage (6.9 months for VFL + BSC v 4.6 months for BSC) was achieved (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12) but was not statistically significant (P = .287). Multivariate Cox analysis adjusting for prognostic factors showed statistically significant effect of VFL on OS (P = .036), reducing the death risk by 23% (HR = 0.77; 95% CI, 0.61 to 0.98). In the eligible population (n = 357), the median OS was significantly longer for VFL + BSC than BSC (6.9 v 4.3 months, respectively), with the difference being statistically significant (P = .040). Overall response rate, disease control, and progression-free survival were all statistically significant favoring VFL + BSC (P = .006, P = .002, and P = .001, respectively).

Conclusion VFL demonstrates a survival advantage in second-line treatment for advanced TCCU. Consistency of results exists with significant and meaningful benefit over all efficacy parameters. Safety profile is acceptable, and therefore, VFL seems to be a reasonable option for TCCU progressing after first-line platinum-based therapy.

Supported by Pierre Fabre, Paris, France.

Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL, and at the 33rd Congress of the European Society for Medical Oncology, September 12-16, 2008, Stockholm, Sweden.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00315237 [ClinicalTrials.gov] .

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