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DeMatteo RP , Ballman KV , Antonescu CR , Maki RG , Pisters PWT , Demetri GD , Blackstein ME , Blanke CD , von Mehren M , Brennan MF , Patel S , McCarter MD , Polikoff JA , Tan BR , Owzar K , ACOSOG Intergrp Adjuvant GIST Stud
Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial
Lancet. 2009 Mar-Apr;373(9669) :1097-1104
PMID: 19303137    PMCID: PMC2915459    URL: https://www.ncbi.nlm.nih.gov/pubmed/19303137
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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 a proteins, and is effective in first-fine 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. Findings 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. Interpretation Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after the resection of primary gastrointestinal stromal tumour. Funding US National Institutes of Health and Novartis Pharmaceuticals.
Notes
ISI Document Delivery No.: 427IS DeMatteo, Ronald P. Ballman, Karla V. Antonescu, Cristina R. Maki, Robert G. Pisters, Peter W. T. Demetri, George D. Blackstein, Martin E. Blanke, Charles D. von Mehren, Margaret Brennan, Murray F. Patel, Shreyaskumar McCarter, Martin D. Polikoff, Jonathan A. Tan, Benjamin R. Owzar, Kouros ELSEVIER SCIENCE INC