• Hagop Kantarjian, Francis Giles, Lydia Wunderle, Kapil Bhalla, Susan O'Brien, Barbara Wassmann, Chiaki Tanaka, Paul Manley, Patricia Rae, William Mietlowski, Kathy Bochinski, Andreas Hochhaus, James D Griffin, Dieter Hoelzer, Maher Albitar, Margaret Dugan, Jorge Cortes, Leila Alland, and Oliver G Ottmann.
• Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1402, USA. hkantarj@mdanderson.org
• N. Engl. J. Med. 2006 Jun 15; 354 (24): 2542-51.

BackgroundResistance 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.MethodsIn 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.ResultsCommon 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.ConclusionsNilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML. (ClinicalTrials.gov number, NCT00109707 [ClinicalTrials.gov].).Copyright 2006 Massachusetts Medical Society.

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