Hagop KantarjianRicardo PasquiniVincent LévySaengsuree JootarJerzy HolowieckiNelson HamerschlakTimothy HughesEric BleickardtDavid DejardinJorge CortesNeil P. ShahUniversity of Texas MD Anderson Cancer CenterHospital de Clínicas de CuritibaHopital Saint-LouisMahidol UniversityUniversity Hospital-SPSKMHospital Israelita Albert EinsteinInstitute of Medical and Veterinary Science AustraliaBristol-Myers SquibbUCSF School of Medicine2018-09-132018-09-132009-09-15Cancer. Vol.115, No.18 (2009), 4136-4147109701420008543X2-s2.0-70149105272https://repository.li.mahidol.ac.th/handle/123456789/27142BACKGROUND: In patients with chronic-phase chronic myeloid leukemia (CP-CML), imatinib resistance is of increasing importance. Imatinib dose escalation was the main treatment option before dasatinib, which has 325-fold more potent inhibition than imatinib against unmutated Bcr-Abl in vitro. Data with a minimum of 2 years of follow-up were available for the current study of dasatinib and high-dose imatinib in CP-CML resistant to imatinib at daily doses from 400 mg to 600 mg. METHODS: A phase 2, open-label study was initiated of 150 patients with imatinib-resistant CP-CML who were randomized (2:1) to receive either dasatinib 70 mg twice daily (n = 101) or high-dose imatinib 800 mg (400 mg twice daily; n = 49). RESULTS: At a minimum follow-up of 2 years, dasatinib demonstrated higher rates of complete hematologic response (93% vs 82%; P = .034), major cytogenetic response (MCyR) (53% vs 33%; P = .017), and complete cytogenetic response (44% vs 18%; P = .0025). At 18 months, the MCyR was maintained in 90% of patients on the dasatinib arm and in 74% of patients on the high-dose imatinib arm. Major molecular response rates also were more frequent with dasatinib than with high-dose imatinib (29% vs 12%; P = .028). The estimated progression-free survival also favored dasatinib (unstratified log-rank test; P = .0012). CONCLUSIONS: After 2 years of follow-up, dasatinib demonstrated durable responses and improved response and progressionfree survival rates relative to high-dose imatinib. © 2009 American Cancer Society.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1002/cncr.24504