Optimizing the dose of imatinib for treatment of gastrointestinal stromal tumours: lessons from the phase 3 trials.

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.