TY - JOUR
T1 - Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL
AU - Kantarjian, Hagop
AU - Giles, Francis
AU - Wunderle, Lydia
AU - Bhalla, Kapil
AU - O'Brien, Susan
AU - Wassmann, Barbara
AU - Tanaka, Chiaki
AU - Manley, Paul
AU - Rae, Patricia
AU - Mietlowski, William
AU - Bochinski, Kathy
AU - Hochhaus, Andreas
AU - Griffin, James D.
AU - Hoelzer, Dieter
AU - Albitar, Maher
AU - Dugan, Margaret
AU - Cortes, Jorge
AU - Alland, Leila
AU - Ottmann, Oliver G.
PY - 2006/6/15
Y1 - 2006/6/15
N2 - BACKGROUND: Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50. METHODS: In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily. RESULTS: Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission. CONCLUSIONS: Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML.
AB - BACKGROUND: Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50. METHODS: In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily. RESULTS: Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission. CONCLUSIONS: Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML.
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U2 - 10.1056/NEJMoa055104
DO - 10.1056/NEJMoa055104
M3 - Article
C2 - 16775235
AN - SCOPUS:33745086350
SN - 0028-4793
VL - 354
SP - 2542
EP - 2551
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 24
ER -