Journal Article

Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy

Baccarani, M, Shou, Y, Kim, D-W, Mendrek, W, Mahon, F-X, Gallagher, N J, Goldberg, S, Rosti, G, Bhatia, R, Kam, G L S, Fischer, T, Jagasia, M, Bosly, A, Cortes, J, Facon, T, Marin, D, Larson, R A, Mueller, M C, Abruzzese, E, Giles, F J, Dünzinger, U, Kantarjian, H M

2010

Overview

Nilotinib is a highly selective Bcr–Abl inhibitor approved for imatinib-resistant chronic myeloid leukemia (CML). Nilotinib and dasatinib, a multi-targeted kinase inhibitor also approved for second-line therapy in CML, have different patterns of kinase selectivity, pharmacokinetics, and cell uptake and efflux properties, and thus patients may respond to one following failure of the other. An international phase II study of nilotinib was conducted in CML patients (39 chronic phase (CP), 21 accelerated phase (AP)) after failure of both imatinib and dasatinib. Median times from diagnosis of CP or AP to nilotinib therapy were 89 and 83 months, respectively. Complete hematological response and major cytogenetic response (MCyR) rates in CP were 79% and 43%, respectively. Of 17 evaluable patients with CML-AP, 5 (29%) had a confirmed hematological response and 2 (12%) a MCyR. The median time to progression has not yet been reached in CP patients. At 18 months 59% of patients were progression-free. Median overall survival for both populations has not been reached, and the estimated 18-month survival rate in CML-CP was 86% and that at 12 months for CML-AP was 80%. Nilotinib is an effective therapy in CML-CP and -AP following failure of both imatinib and dasatinib therapy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/92/436/1729 / 692/699/67/1990/283/1896 / 692/700/1750 / 692/700/565/1436/99 / Adult / Aged / Antimitotic agents / Antineoplastic agents / BCR-ABL protein / Benzamides / Biological and medical sciences / Cancer Research / Chronic myeloid leukemia / Critical Care Medicine / Cytogenetics / Dasatinib / Dosage and administration / Drug Resistance, Neoplasm / Drug therapy / Efflux / Enzyme inhibitors / Failure / Female / Hematologic and hematopoietic diseases / Hematology / Humans / Imatinib / Imatinib Mesylate / Inhibitor drugs / Intensive / Internal Medicine / International Agencies / Kinases / Leukemia / Leukemia, Myeloid, Accelerated Phase - drug therapy / Leukemia, Myeloid, Accelerated Phase - mortality / Leukemia, Myeloid, Chronic-Phase - drug therapy / Leukemia, Myeloid, Chronic-Phase - mortality / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Male / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Myeloid leukemia / Oncology / original-article / Patient outcomes / Pharmacokinetics / Piperazines - therapeutic use / Protein-Tyrosine Kinases - antagonists & inhibitors / Pyrimidines - therapeutic use / Salvage Therapy / Selectivity / Survival / Survival Rate / Targeted cancer therapy / Therapy / Thiazoles - therapeutic use / Treatment Outcome / Young Adult