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

Cortes, A.Baccarani, M.Guilhot, F.Druker, B.Branford, S.Kim, D.Pane, F.Pasquini, R.Goldberg, S.Kalaycio, M.Moiraghi, B.Rowe, J.Tothova, E.de Souza, C.Rudoltz, M.Yu, R.Krahnke, T.Kantarjian, H.Radich, J.Hughes, T.2011-05-272011-05-272010Journal of Clinical Oncology, 2010; 28(3):424-4300732-183X1527-7755http://hdl.handle.net/2440/63998Purpose: 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.en© 2009 by American Society of Clinical OncologyHumansLeukemia, Myeloid, Chronic-PhaseBenzamidesPiperazinesPyrimidinesAntineoplastic AgentsProtein Kinase InhibitorsTreatment OutcomeDose-Response Relationship, DrugAdolescentAdultAgedMiddle AgedFemaleMaleProtein-Tyrosine KinasesYoung AdultImatinib MesylatePhase 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 StudyJournal article002010013210.1200/JCO.2009.25.37240002736627000122-s2.0-7574910588533781Branford, S. [0000-0002-1964-3626] [0000-0002-5095-7981]Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]