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.
BJU Int
; 126(2): 292-299, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32336008
ABSTRACT
OBJECTIVES:
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. PATIENTS ANDMETHODS:
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/m2 days 1 and 8) combined with either oral vandetanib 100 mg or placebo (once daily). Progression-free survival (PFS; primary endpoint), adverse events, tolerability and feasibility of use, objective response rate and overall survival (OS) were evaluated. Intention-to-treat and per-protocol analyses were used to analyse the primary endpoint.RESULTS:
The 82 patients were randomised 11 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%.CONCLUSION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Quinazolinas
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Carcinoma de Células de Transição
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Protocolos de Quimioterapia Combinada Antineoplásica
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Carboplatina
/
Desoxicitidina
Tipo de estudo:
Clinical_trials
/
Guideline
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
BJU Int
Assunto da revista:
UROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido