Juan W. Valle
Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial
Valle, Juan W.; Wasan, Harpreet; Lopes, Andre; Backen, Alison C.; Palmer, Daniel H.; Morris, Karen; Duggan, Marian; Cunningham, David; Anthoney, D. Alan; Corrie, Pippa; Srinivasan, Narayanan; Maraveyas, Anthony; Ross, Paul J.; Waters, Justin S.; Steward, Will P.; Rees, Charlotte; Beare, Sandy; Dive, Caroline; Bridgewater, John A.
Authors
Harpreet Wasan
Andre Lopes
Alison C. Backen
Daniel H. Palmer
Karen Morris
Marian Duggan
David Cunningham
D. Alan Anthoney
Pippa Corrie
SRINIVASAN MADHUSUDAN srinivasan.madhusudan@nottingham.ac.uk
Professor of Medical Oncology
Anthony Maraveyas
Paul J. Ross
Justin S. Waters
Will P. Steward
Charlotte Rees
Sandy Beare
Caroline Dive
John A. Bridgewater
Abstract
BACKGROUND: Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addition of cediranib (an oral inhibitor of VEGF receptor 1, 2, and 3) to cisplatin and gemcitabine on progression-free survival.
METHODS: In this multicentre, placebo-controlled, randomised phase 2 study, we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK. Patients were eligible if they had an ECOG performance status of 0-1 and an estimated life expectancy of longer than 3 months. Patients were given first-line cisplatin and gemcitabine chemotherapy (25 mg/m(2) cisplatin and 1000 mg/m(2) gemcitabine [on days 1 and 8 every 21 days, for up to eight cycles]) with either 20 mg oral cediranib or placebo once a day until disease progression. We randomly assigned patients (1:1) with a minimisation algorithm, incorporating the stratification factors: extent of disease, primary disease site, previous treatment, ECOG performance status, and centre. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00939848, and was closed on Sept 30, 2014; results of the final analysis for the primary endpoint are presented.
FINDINGS: Between April 5, 2011, and Sept 28, 2012, we enrolled 124 patients (62 in each group). With a median follow-up of 12·2 months (IQR 7·3-18·5), median progression-free survival was 8·0 months (95% CI 6·5-9·3) in the cediranib group and 7·4 months (5·7-8·5) in the placebo group (HR 0·93, 80% CI 0·74-1·19, 95% CI 0·65-1·35; p=0·72). Patients who received cediranib had more grade 3-4 toxic effects than did patients who received placebo: hypertension (23 [37%] vs 13 [21%]; p=0·05), diarrhoea (eight [13%] vs two [3%]; p=0·05); platelet count decreased (ten [16%] vs four [6%]; p=0·09), white blood cell decreased (15 [24%] vs seven [11%]; p=0·06) and fatigue (16 [24%] vs seven [11%]; p=0·04).
INTERPRETATION: Cediranib did not improve the progression-free survival of patients with advanced biliary tract cancer in combination with cisplatin and gemcitabine, which remains the standard of care. Although patients in the cediranib group had more adverse events, we recorded no unexpected toxic effects. The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational.
Citation
Valle, J. W., Wasan, H., Lopes, A., Backen, A. C., Palmer, D. H., Morris, K., …Bridgewater, J. A. (2015). Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. Lancet Oncology, 16(8), https://doi.org/10.1016/S1470-2045%2815%2900139-4
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 1, 2015 |
Online Publication Date | Jul 12, 2015 |
Publication Date | Aug 1, 2015 |
Deposit Date | May 24, 2017 |
Publicly Available Date | May 24, 2017 |
Journal | Lancet Oncology |
Print ISSN | 1470-2045 |
Electronic ISSN | 1474-5488 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 16 |
Issue | 8 |
DOI | https://doi.org/10.1016/S1470-2045%2815%2900139-4 |
Public URL | https://nottingham-repository.worktribe.com/output/755785 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S1470204515001394 |
Contract Date | May 24, 2017 |
Files
lancet_oncology_2015_1.pdf
(595 Kb)
PDF
Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
You might also like
The role of the ALKBH5 RNA demethylase in invasive breast cancer
(2024)
Journal Article
Epitranscriptomic mechanisms of androgen signalling and prostate cancer
(2024)
Journal Article
The characteristics and prognostic significance of histone H1 expression in breast cancer
(2024)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search