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Phase III , randomized , open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed , previously untreated chronic myeloid leukemia in chronic phase using molecular end points : tyrosine kinase inhibitor optimization and selectivity study . PURPOSE To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d ( 400 mg twice daily ) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase . PATIENTS AND METHODS A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg ( n = 319 ) or 400 mg ( n = 157 ) daily . The primary end point was the major molecular response ( MMR ) rate at 12 months . RESULTS At 12 months , differences in MMR and complete cytogenetic response ( CCyR ) rates were not statistically significant ( MMR , 46 % v 40 % ; P = .2035 ; CCyR , 70 % v 66 % ; P = .3470 ) . However , MMR occurred faster among patients randomly assigned to imatinib 800 mg/d , who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm ( P = .0035 by log-rank test ) . CCyR also occurred faster in the 800-mg/d arm ( CCyR at 6 months , 57 % v 45 % ; P = .0146 ) . The most common adverse events were edema , gastrointestinal problems , and rash , and all were more common in patients in the 800-mg/d arm . Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d . CONCLUSION MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d , but MMR and CCyR occurred earlier in patients treated with 800 mg/d . Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib .
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Intervention_Pharmacological
imatinib mesylate
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Intervention_Pharmacological
imatinib mesylate
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Intervention_Pharmacological
imatinib 800 mg
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Intervention_Pharmacological
or 400 mg
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Intervention_Pharmacological
imatinib
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Intervention_Pharmacological
imatinib .
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Outcome_Physical
major molecular response ( MMR ) rate
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Outcome_Physical
MMR and complete cytogenetic response ( CCyR ) rates
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Outcome_Physical
MMR
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Outcome_Physical
MMR
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Outcome_Physical
CCyR
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Outcome_Adverse-effects
edema , gastrointestinal problems , and rash
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Outcome_Adverse-effects
Grades 3 to 4 hematologic toxicity
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Outcome_Physical
MMR and CCyR