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document
Approval summary : imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors . The purpose of the present application was to fulfill a postmarketing commitment to provide long-term efficacy and safety data on treatment with imatinib mesylate ( Gleevec ; Novartis Pharmaceuticals , East Hanover , NJ ) in patients with CD117 ( + ) unresectable and/or metastatic malignant gastrointestinal stromal tumors ( GISTs ) . In addition , this application also provides evidence to support a change in the label to allow for an escalation of imatinib dosing to 800 mg/day for patients with progressive disease on a lower dose . Two open-label , controlled , multicenter , intergroup , international , randomized phase III studies were submitted -- one conducted by the European Organization for Research and Treatment of Cancer ( n = 946 ) and the other by the Southwest Oncology Group ( n = 746 ) . These studies compared 400 mg/day of imatinib with 800 mg/day of imatinib . A combined analysis of the two studies was prospectively defined and agreed to by both groups . Both protocols allowed patients randomized to the 400-mg/day imatinib arm to cross over to 800 mg/day imatinib at progression . Objective responses were achieved in > 50 % of patients receiving either imatinib dose . The median progression-free survival time was approximately 20 months and the median overall survival ( OS ) time was approximately 49 months . In the combined analysis , 347 patients crossed over to 800 mg/day imatinib at the time of progression . The median OS time after crossover was 14.3 months . The most common adverse events ( AEs ) were fluid retention , nausea , fatigue , skin rash , gastrointestinal complaints , and myalgia . The most common laboratory abnormality was anemia . Most often the AEs were of mild-to-moderate severity . Fluid retention events and skin rash were numerically reported more often in the 800-mg/day treatment cohort of patients .
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Intervention_Pharmacological
imatinib mesylate
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Intervention_Pharmacological
imatinib mesylate
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Intervention_Pharmacological
imatinib
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Intervention_Pharmacological
imatinib
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Intervention_Pharmacological
imatinib
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Intervention_Pharmacological
imatinib
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Intervention_Pharmacological
imatinib
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Intervention_Pharmacological
imatinib
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Intervention_Pharmacological
imatinib
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Outcome_Physical
imatinib mesylate
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Outcome_Physical
imatinib
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Outcome_Mortality
progression-free survival time
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Outcome_Physical
median OS
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Outcome_Adverse-effects
adverse events ( AEs )
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Outcome_Adverse-effects
nausea , fatigue , skin rash , gastrointestinal complaints , and myalgia
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Outcome_Adverse-effects
abnormality was anemia .
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Outcome_Physical
AEs
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Participant_Condition
malignant gastrointestinal stromal tumors
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Participant_Condition
GISTs
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Participant_Sample-size
946
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Participant_Sample-size
746