Abstract
Dasatinib is the most potent BCR-ABL inhibitor, with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Studies have demonstrated the benefits of dasatinib 70 mg twice daily in patients with accelerated-phase chronic myeloid leukemia intolerant or resistant to imatinib. A phase 3 study compared the efficacy and safety of dasatinib 140 mg once daily with the current twice-daily regimen. Here, results from the subgroup with accelerated-phase chronic myeloid leukemia (n = 317) with a median follow-up of 15 months (treatment duration, 0.03-31.15 months) are reported. Among patients randomized to once-daily (n = 158) or twice-daily (n = 159) treatment, rates of major hematologic and cytogenetic responses were comparable (major hematologic response, 66% vs 68%; major cytogenetic response, 39% vs 43%, respectively). Estimated progression-free survival rates at 24 months were 51% and 55%, whereas overall survival rates were 63% versus 72%. Once-daily treatment was associated with an improved safety profile. In particular, significantly fewer patients in the once-daily group experienced a pleural effusion (all grades, 20% vs 39% P < .001). These results demonstrate that dasatinib 140 mg once daily has similar efficacy to dasatinib 70 mg twice daily but with an improved safety profile. This trial is registered at www.clinicaltrials.gov as #CA180-035.
Trial registration:
ClinicalTrials.gov NCT00123487.
Publication types
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Clinical Trial, Phase III
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / therapeutic use*
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Benzamides
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Dasatinib
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Drug Resistance, Neoplasm
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Female
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Follow-Up Studies
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Fusion Proteins, bcr-abl / analysis
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Fusion Proteins, bcr-abl / genetics
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Gastrointestinal Diseases / chemically induced
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Genes, abl
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Heart Diseases / chemically induced
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Hematologic Diseases / chemically induced
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Humans
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Imatinib Mesylate
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Kaplan-Meier Estimate
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Leukemia, Myeloid, Accelerated Phase / drug therapy*
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Leukemia, Myeloid, Accelerated Phase / genetics
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Male
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Middle Aged
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Mutation
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Piperazines / adverse effects
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Piperazines / pharmacology
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Pyrimidines / administration & dosage
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Pyrimidines / adverse effects
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Pyrimidines / pharmacology
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Pyrimidines / therapeutic use*
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Thiazoles / administration & dosage
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Thiazoles / adverse effects
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Thiazoles / therapeutic use*
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Young Adult
Substances
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Antineoplastic Agents
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Benzamides
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Thiazoles
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Imatinib Mesylate
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Fusion Proteins, bcr-abl
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Dasatinib
Associated data
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ClinicalTrials.gov/NCT00123487