Document Detail


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.
MedLine Citation:
PMID:  19687335     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 Th?odore; Tomasz Demkov; Boris Komyakov; Lisa Sengelov; Gedske Daugaard; Armelle Caty; Joan Carles; Agnieszka Jagiello-Gruszfeld; Oleg Karyakin; Fran?ois-Michel Delgado; Patrick Hurteloup; Eric Winquist; Nassim Morsli; Yacine Salhi; St?phane Culine; Hans von der Maase
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Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-08-17
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  27     ISSN:  1527-7755     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-10-02     Completed Date:  2009-11-04     Revised Date:  2010-05-03    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4454-61     Citation Subset:  IM    
Affiliation:
Department of Medical Oncology, University Hospital Del Mar, Passeig Mar?tim 25-29, E-08003 Barcelona, Spain. jbellmunt@imas.imim.es
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MeSH Terms
Descriptor/Qualifier:
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*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Platinum Compounds; 162652-95-1/vinflunine; 865-21-4/Vinblastine
Comments/Corrections
Comment In:
J Clin Oncol. 2010 May 1;28(13):e205-7; author reply e208   [PMID:  20159797 ]
J Clin Oncol. 2009 Sep 20;27(27):4444-5   [PMID:  19687324 ]
Erratum In:
J Clin Oncol. 2010 Jan 1;28(1):182
Note: Winquist, Eric [added]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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