A randomised Phase II trial of carboplatin and gemcitabine ± vandetanib in first-line treatment of patients with advanced urothelial cell cancer not suitable to receive cisplatin.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Carboplatin
/ administration & dosage
Carcinoma, Transitional Cell
/ drug therapy
Cisplatin
Deoxycytidine
/ administration & dosage
Double-Blind Method
Drug Combinations
Female
Humans
Male
Neoplasm Staging
Piperidines
/ administration & dosage
Quinazolines
/ administration & dosage
Treatment Outcome
Gemcitabine
carboplatin
gemcitabine
randomised controlled trial
tyrosine kinase inhibitor
urothelial carcinoma
vandetanib
Journal
BJU international
ISSN: 1464-410X
Titre abrégé: BJU Int
Pays: England
ID NLM: 100886721
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
27
4
2020
medline:
18
12
2020
entrez:
27
4
2020
Statut:
ppublish
Résumé
To assess the efficacy and tolerability of the dual epidermal growth factor receptor/vascular endothelial growth factor receptor inhibitor, vandetanib, in combination with carboplatin and gemcitabine in the first-line treatment of patients with advanced transitional cell carcinoma urothelial cancer (UC) who were unsuitable for cisplatin. From 2011 to 2014, 82 patients were randomised from 16 hospitals across the UK into the TOUCAN double-blind, placebo-controlled randomised Phase II trial, receiving six 21-day cycles of intravenous carboplatin (target area under the concentration versus time curve 4.5, day 1) and gemcitabine (1000 mg/m The 82 patients were randomised 1:1 to vandetanib (n = 40) or placebo (n = 42), and 25 patients (30%) completed six cycles of all allocated treatment. Toxicity Grade ≥3 was experienced in 80% (n = 32) and 76% (n = 32) of patients in the vandetanib and placebo arms, respectively. The median PFS was 6.8 and 8.8 months for the vandetanib and placebo arms, respectively (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.65-1.76; P = 0.71); the median OS was 10.8 vs 13.8 months (HR 1.41, 95% CI 0.79-2.52; P = 0.88); and radiological response rates were 50% and 55%. There is no evidence that vandetanib improves clinical outcome in this setting. Our present data do not support its adoption as the regimen of choice for first-line treatment in patients with UC who were unfit for cisplatin.
Substances chimiques
Drug Combinations
0
Piperidines
0
Quinazolines
0
Deoxycytidine
0W860991D6
Carboplatin
BG3F62OND5
Cisplatin
Q20Q21Q62J
vandetanib
YO460OQ37K
Gemcitabine
0
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
292-299Subventions
Organisme : Cancer Research UK
ID : CRUKE/09/024
Pays : United Kingdom
Informations de copyright
© 2020 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International.
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