Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL
| Autor: | Paul W. Manley, Andreas Hochhaus, James D. Griffin, Barbara Wassmann, Kapil N. Bhalla, Susan O'Brien, Oliver G. Ottmann, Kathy Bochinski, Maher Albitar, Lydia Wunderle, Dieter Hoelzer, Patricia Rae, Leila Alland, Hagop M. Kantarjian, Francis J. Giles, Jorge E. Cortes, William Mietlowski, Chiaki Tanaka, Margaret Dugan |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Fusion Proteins bcr-abl Antineoplastic Agents Blastic Phase Philadelphia chromosome Gastroenterology Piperazines hemic and lymphatic diseases Acute lymphocytic leukemia Internal medicine Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Protein Kinase Inhibitors Aged Aged 80 and over business.industry Imatinib General Medicine Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Protein-Tyrosine Kinases medicine.disease Hematologic Response Imatinib mesylate Pyrimidines Nilotinib Drug Resistance Neoplasm Benzamides Cancer research Imatinib Mesylate Female business Chronic myelogenous leukemia medicine.drug |
| Zdroj: | The New England journal of medicine. 354(24) |
| ISSN: | 1533-4406 |
| Popis: | 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.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.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.Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML. (ClinicalTrials.gov number, NCT00109707 [ClinicalTrials.gov].). |
| Databáze: | OpenAIRE |
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