title: Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first-line treatment of metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after resection of localised, primary gastrointestinal stromal tumour.
  
  
  METHODS
  We undertook a randomised phase III, double-blind, placebo-controlled, multicentre trial. Eligible patients had complete gross resection of a primary gastrointestinal stromal tumour at least 3 cm in size and positive for the KIT protein by immunohistochemistry. Patients were randomly assigned, by a stratified biased coin design, to imatinib 400 mg (n=359) or to placebo (n=354) daily for 1 year after surgical resection. Patients and investigators were blinded to the treatment group. Patients assigned to placebo were eligible to crossover to imatinib treatment in the event of tumour recurrence. The primary endpoint was recurrence-free survival, and analysis was by intention to treat. Accrual was stopped early because the trial results crossed the interim analysis efficacy boundary for recurrence-free survival. This study is registered with ClinicalTrials.gov, number NCT00041197.
  
  
  RESULTS
  All randomised patients were included in the analysis. At median follow-up of 19.7 months (minimum-maximum 0-56.4), 30 (8%) patients in the imatinib group and 70 (20%) in the placebo group had had tumour recurrence or had died. Imatinib significantly improved recurrence-free survival compared with placebo (98% [95% CI 96-100] vs 83% [78-88] at 1 year; hazard ratio [HR] 0.35 [0.22-0.53]; one-sided p<0.0001). Adjuvant imatinib was well tolerated, with the most common serious events being dermatitis (11 [3%] vs 0), abdominal pain (12 [3%] vs six [1%]), and diarrhoea (ten [2%] vs five [1%]) in the imatinib group and hyperglycaemia (two [<1%] vs seven [2%]) in the placebo group.
  
  
  CONCLUSIONS
  Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after the resection of primary gastrointestinal stromal tumour.
  
  
  BACKGROUND
  US National Institutes of Health and Novartis Pharmaceuticals.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Dematteo
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
authors.forename: Peter W T
authors.initials: PW
authors.lastname: Pisters
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.forename: Martin E
authors.initials: ME
authors.lastname: Blackstein
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.forename: Murray F
authors.initials: MF
authors.lastname: Brennan
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.forename: Martin D
authors.initials: MD
authors.lastname: McCarter
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Polikoff
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Tan
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate