title: TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG).
abstract: BACKGROUND
  The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy. We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy.
  
  
  METHODS
  Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given. The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique.
  
  
  CONCLUSIONS
  TOPGEAR is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry: ACTRN12609000035224 . Registered 30 May 2009.
authors.affiliation: Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Victoria, 8006, Australia. Trevor.Leong@petermac.org.
authors.forename: Trevor
authors.initials: T
authors.lastname: Leong
authors.affiliation: Upper Gastro-intestinal and Soft Tissue Unit, School of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD, 4102, Australia. m.smithers@uq.edu.au.
authors.forename: B Mark
authors.initials: BM
authors.lastname: Smithers
authors.affiliation: Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Victoria, 8006, Australia. Michael.Michael@petermac.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Locked bag 77, Camperdown, NSW, 1450, Australia. val@ctc.usyd.edu.au.
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.affiliation: Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Victoria, 8006, Australia. alex.boussioutas@petermac.org.
authors.forename: Alex
authors.initials: A
authors.lastname: Boussioutas
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Locked bag 77, Camperdown, NSW, 1450, Australia. danielle.miller@ctc.usyd.edu.au.
authors.forename: Danielle
authors.initials: D
authors.lastname: Miller
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Locked bag 77, Camperdown, NSW, 1450, Australia. john@ctc.usyd.edu.au.
authors.forename: John
authors.initials: J
authors.lastname: Simes
authors.affiliation: School of Public Health and Preventive Medicine, Monash University, Level 5 The Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia. john.zalcberg@monash.edu.
authors.forename: John
authors.initials: J
authors.lastname: Zalcberg
authors.affiliation: Radiation Oncology, University Hospitals Leuven, Department of Oncology, KU, Leuven, Belgium. karin.haustermans@uzleuven.be.
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
authors.affiliation: University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Leipzig, Germany. florian.lordick@medizin.uni-leipzig.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.affiliation: European Clinical Research Infrastructure Network, ECRIN-ERIC, Paris Biopark, 5 rue Watt, 75013, Paris, France. christoph.schuhmacher@ecrin.org.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schuhmacher
authors.affiliation: Mount Sinai Hospital, Rm 1225, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. cswallow@mtsinai.on.ca.
authors.forename: Carol
authors.initials: C
authors.lastname: Swallow
authors.affiliation: Toronto General Hospital, 9N-955, 200 Elizabeth St, Toronto, ON, M5G 2C4, Canada. Gail.Darling@uhn.ca.
authors.forename: Gail
authors.initials: G
authors.lastname: Darling
authors.affiliation: Princess Margaret Hospital, Rm 5-807, 610 University Avenue, Toronto, M5G 2M9, Canada. Rebecca.Wong@rmp.uhn.on.ca.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wong
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D015251:Epirubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004943:Esophagogastric Junction / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D019990:Perioperative Care; D011300:Preoperative Care; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil