26179201
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 .
BACKGROUND	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 .
METHODS	Patients were eligible if they had an ECOG performance status of 0-1 and an estimated life expectancy of longer than 3 months .
METHODS	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 .
METHODS	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 .
METHODS	The primary endpoint was progression-free survival in the intention-to-treat population .
METHODS	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 .
RESULTS	Between April 5 , 2011 , and Sept 28 , 2012 , we enrolled 124 patients ( 62 in each group ) .
RESULTS	With a median follow-up of 122 months ( IQR 73-185 ) , median progression-free survival was 80 months ( 95 % CI 65-93 ) in the cediranib group and 74 months ( 57-85 ) in the placebo group ( HR 093 , 80 % CI 074-119 , 95 % CI 065-135 ; p = 072 ) .
RESULTS	Patients who received cediranib had more grade 3-4 toxic effects than did patients who received placebo : hypertension ( 23 [ 37 % ] vs 13 [ 21 % ] ; p = 005 ) , diarrhoea ( eight [ 13 % ] vs two [ 3 % ] ; p = 005 ) ; platelet count decreased ( ten [ 16 % ] vs four [ 6 % ] ; p = 009 ) , white blood cell decreased ( 15 [ 24 % ] vs seven [ 11 % ] ; p = 006 ) and fatigue ( 16 [ 24 % ] vs seven [ 11 % ] ; p = 004 ) .
CONCLUSIONS	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 .
CONCLUSIONS	Although patients in the cediranib group had more adverse events , we recorded no unexpected toxic effects .
CONCLUSIONS	The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational .
BACKGROUND	Cancer Research UK and AstraZeneca Pharmaceuticals .

