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.

Abstract

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/m(2), every 3 weeks; PS = 0 with previous pelvic radiation and PS = 1: 280 mg/m(2) subsequently escalated to 320 mg/m(2)) 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.

• Authors: Joaquim Bellmunt, Christine Théodore, Tomasz Demkov, Boris Komyakov, Lisa Sengelov, Gedske Daugaard, Armelle Caty, Joan Carles, Agnieszka Jagiello-Gruszfeld, Oleg Karyakin, François-Michel Delgado, Patrick Hurteloup, Eric Winquist, Nassim Morsli, Yacine Salhi, Stéphane Culine, Hans von der Maase
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 27 Pg. 4454-61 (Sep 20 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19687335 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Platinum Compounds
• vinflunine
• Vinblastine

Topics

• Aged
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Transitional Cell (drug therapy, secondary)
• Disease Progression
• Humans
• Middle Aged
• Palliative Care
• Platinum Compounds (administration & dosage)
• Survival Analysis
• Urologic Neoplasms (drug therapy, secondary)
• Urothelium (pathology)
• Vinblastine (administration & dosage, analogs & derivatives)