Abstract
Imatinib therapy for unresectable or metastatic gastrointestinal stromal tumour (GIST) is typically initiated at a dosage of 400mg/d. Two phase 3 studies investigated whether the higher dose of 800 mg/d - administered initially or upon progression on the 400-mg dose - would improve outcomes. Both the studies confirmed the 400mg/d starting dose for most patients. However, two groups benefited from the treatment with 800 mg/d of imatinib: patients with disease progression on standard-dose therapy, and patients whose tumour harbours an exon 9 mutation in KIT. Initial treatment with 800 mg/d of imatinib (400mg BID) should be considered for patients with KIT exon 9-mutant GIST. In unselected patients, dose optimisation to 800 mg/d may be warranted as a first step in managing progressive disease; such patients should be closely monitored.
Publication types
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Meta-Analysis
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adolescent
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Adult
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Aged
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Antineoplastic Agents / administration & dosage*
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Benzamides
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Clinical Trials, Phase III as Topic
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Disease Progression
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Disease-Free Survival
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Dose-Response Relationship, Drug
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Female
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Gastrointestinal Stromal Tumors / drug therapy*
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Gastrointestinal Stromal Tumors / genetics
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Gastrointestinal Stromal Tumors / mortality
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Humans
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Imatinib Mesylate
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Male
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Middle Aged
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Multicenter Studies as Topic
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Mutation / genetics
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Piperazines / administration & dosage*
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Proto-Oncogene Proteins c-kit / genetics
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Pyrimidines / administration & dosage*
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Randomized Controlled Trials as Topic
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Receptor, Platelet-Derived Growth Factor alpha / genetics
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Treatment Outcome
Substances
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Antineoplastic Agents
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Benzamides
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Piperazines
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Pyrimidines
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Imatinib Mesylate
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Proto-Oncogene Proteins c-kit
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Receptor, Platelet-Derived Growth Factor alpha