title: A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study.
abstract: BACKGROUND
  The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC.
  
  
  METHODS
  Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes.
  
  
  RESULTS
  A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm).
  
  
  CONCLUSIONS
  Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs.
  
  
  BACKGROUND
  NCT00753675.
authors.affiliation: Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan armando.santoro@cancercenter.humanitas.it.
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Department of Medical Oncology, Nursing Home 'La Maddalena', Palermo.
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.affiliation: Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan.
authors.forename: T
authors.initials: T
authors.lastname: Pressiani
authors.affiliation: Department of Medical Oncology, Nursing Home 'La Maddalena', Palermo.
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.affiliation: Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan.
authors.forename: N
authors.initials: N
authors.lastname: Personeni
authors.affiliation: Department of Medical Oncology, Nursing Home 'La Maddalena', Palermo.
authors.forename: E
authors.initials: E
authors.lastname: Arrivas Bajardi
authors.affiliation: Department of Medical Oncology, 'San Paolo' University Hospital, Milan.
authors.forename: P
authors.initials: P
authors.lastname: Foa
authors.affiliation: Oncology Referral Center, IRCCS, Aviano.
authors.forename: A
authors.initials: A
authors.lastname: Buonadonna
authors.affiliation: Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan.
authors.forename: K
authors.initials: K
authors.lastname: Bencardino
authors.affiliation: Department of Medical Oncology, Università Cattolica del S. Cuore, Rome.
authors.forename: C
authors.initials: C
authors.lastname: Barone
authors.affiliation: Department of Medical Oncology, 'San Paolo' University Hospital, Milan.
authors.forename: D
authors.initials: D
authors.lastname: Ferrari
authors.affiliation: Department of Oncology, 'Poliambulanza' Foundation, Brescia.
authors.forename: A
authors.initials: A
authors.lastname: Zaniboni
authors.affiliation: Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan.
authors.forename: M C
authors.initials: MC
authors.lastname: Tronconi
authors.affiliation: Department of Oncology, Cardarelli Hospital, Naples.
authors.forename: G
authors.initials: G
authors.lastname: Cartenì
authors.affiliation: Medical Oncology A, Regina Elena National Cancer Institute, Rome.
authors.forename: M
authors.initials: M
authors.lastname: Milella
authors.affiliation: Department of Oncology, Gradenigo Hospital, Turin.
authors.forename: A
authors.initials: A
authors.lastname: Comandone
authors.affiliation: Oncology Unit, AstraZeneca, Basiglio, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan.
authors.forename: L
authors.initials: L
authors.lastname: Rimassa
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001661:Biliary Tract Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D000093542:Gemcitabine
chemical_list: D010880:Piperidines; D011799:Quinazolines; D003841:Deoxycytidine; C452423:vandetanib; D000093542:Gemcitabine
keywords: advanced biliary tract cancer; gemcitabine; vandetanib