Nilotinib As Front-Line Treatment for Patients With Chronic Myeloid Leukemia in Early Chronic Phase

被引:189
作者
Cortes, Jorge E. [1 ]
Jones, Dan
O'Brien, Susan
Jabbour, Elias
Konopleva, Marina
Ferrajoli, Alessandra
Kadia, Tapan
Borthakur, Gautam
Stigliano, Denise
Shan, Jianqin
Kantarjian, Hagop
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
关键词
CHRONIC MYELOGENOUS LEUKEMIA; ALPHA PLUS CYTARABINE; IMATINIB MESYLATE; CYTOGENETIC RESPONSES; MOLECULAR RESPONSES; INTERFERON; AMN107; RESISTANCE; BMS-354825; INHIBITOR;
D O I
10.1200/JCO.2009.25.4896
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Although most patients with chronic myeloid leukemia (CML) in chronic phase respond well to front-line therapy with imatinib, some patients do not achieve the desirable end point, and others may eventually lose response or are intolerant. Patients and Methods Patients with newly diagnosed CML in chronic phase were treated with nilotinib 400 mg twice daily on an empty stomach as initial therapy. Results Among 51 patients in chronic phase observed for at least 3 months, 50 (98%) achieved a complete cytogenetic remission (CCyR), and 39 (76%) achieved a major molecular response (MMR). Responses occurred rapidly, with 96% of patients achieving CCyR by 3 months and 98% achieving CCyR by 6 months. The projected event-free survival at 24 months is 90%, and all patients are alive after a median follow-up time of 17 months. Grade >= 3 neutropenia occurred in 12% of patients, and thrombocytopenia in occurred 11%. Nonhematologic toxicity was usually grade 1 to 2 and manageable. The actual median dose at 12 months was 800 mg (range, 200 to 800 mg). Conclusion Nilotinib is an effective option for the initial management of CML in early chronic phase, producing high rates of CCyR and MMR, with most patients reaching these responses early during their therapy.
引用
收藏
页码:392 / 397
页数:6
相关论文
共 24 条
[1]   Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet [J].
Baccarani, Michele ;
Saglio, Giuseppe ;
Goldman, John ;
Hochhaus, Andreas ;
Simonsson, Bengt ;
Appelbaum, Frederick ;
Apperley, Jane ;
Cervantes, Francisco ;
Cortes, Jorge ;
Deininger, Michael ;
Gratwohl, Alois ;
Guilhot, Frangois ;
Horowitz, Mary ;
Hughes, Timothy ;
Kantarjian, Hagop ;
Larson, Richard ;
Niederwieser, Dielger ;
Silver, Richard ;
Hehlmann, Rudiger .
BLOOD, 2006, 108 (06) :1809-1820
[2]   Comparison of imatinib, mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen:: high efficacy of drug combinations [J].
Bradeen, Heather A. ;
Eide, Christopher A. ;
O'Hare, Thomas ;
Johnson, Kara J. ;
Willis, Stephanie G. ;
Lee, Francis Y. ;
Druker, Brian J. ;
Deininger, Michael W. .
BLOOD, 2006, 108 (07) :2332-2338
[3]   Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate [J].
Cortes, J ;
Talpaz, M ;
O'Brien, S ;
Jones, D ;
Luthra, R ;
Shan, J ;
Giles, F ;
Faderl, S ;
Verstovsek, S ;
Garcia-Manero, G ;
Rios, MB ;
Kantarjian, H .
CLINICAL CANCER RESEARCH, 2005, 11 (09) :3425-3432
[4]  
CORTES J, 2008, BLOOD, V112, P1098
[5]  
Cortes Jorge, 2008, J Natl Compr Canc Netw, V6 Suppl 2, pS22
[6]   High-Dose Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: High Rates of Rapid Cytogenetic and Molecular Responses [J].
Cortes, Jorge E. ;
Kantarjian, Hagop M. ;
Goldberg, Stuart L. ;
Powell, Bayard L. ;
Giles, Francis J. ;
Wetzler, Meir ;
Akard, Luke ;
Burke, John M. ;
Kerr, Robert ;
Saleh, Mansoor ;
Salvado, August ;
McDougall, Karen ;
Albitar, Maher ;
Radich, Jerald .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (28) :4754-4759
[7]   Imatinib for newly diagnosed patients with chronic myeloid leukemia: Incidence of sustained responses in an intention-to-treat analysis [J].
de Lavallade, Hugues ;
Apperley, Jane F. ;
Khorashad, Jamshid S. ;
Milojkovic, Dragana ;
Reid, Alistair G. ;
Bua, Marco ;
Szydlo, Richard ;
Olavarria, Eduardo ;
Kaeda, Jaspal ;
Goldman, John M. ;
Marin, David .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (20) :3358-3363
[8]   Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia [J].
Druker, Brian J. ;
Guilhot, Francois ;
O'Brien, Stephen G. ;
Gathmann, Insa ;
Kantarjian, Hagop ;
Gattermann, Norbert ;
Deininger, Michael W. N. ;
Silver, Richard T. ;
Goldman, John M. ;
Stone, Richard M. ;
Cervantes, Francisco ;
Hochhaus, Andreas ;
Powell, Bayard L. ;
Gabrilove, Janice L. ;
Rousselot, Philippe ;
Reiffers, Josy ;
Cornelissen, Jan J. ;
Hughes, Timothy ;
Agis, Hermine ;
Fischer, Thomas ;
Verhoef, Gregor ;
Shepherd, John ;
Saglio, Giuseppe ;
Gratwohl, Alois ;
Nielsen, Johan L. ;
Radich, Jerald P. ;
Simonsson, Bengt ;
Taylor, Kerry ;
Baccarani, Michele ;
So, Charlene ;
Letvak, Laurie ;
Larson, Richard A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (23) :2408-2417
[9]   Time to complete cytogenetic response (CCyR) does not affect long-term outcomes for patients on imatinib therapy [J].
Guilhot, Francois ;
Larson, Richard A. ;
O'Brien, Stephen G. ;
Gathmann, Insa ;
Druker, Brian J. .
BLOOD, 2007, 110 (11) :16A-16A
[10]   Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib [J].
Hochhaus, A. ;
Baccarani, M. ;
Deininger, M. ;
Apperley, J. F. ;
Lipton, J. H. ;
Goldberg, S. L. ;
Corm, S. ;
Shah, N. P. ;
Cervantes, F. ;
Silver, R. T. ;
Niederwieser, D. ;
Stone, R. M. ;
Dombret, H. ;
Larson, R. A. ;
Roy, L. ;
Hughes, T. ;
Mueller, M. C. ;
Ezzeddine, R. ;
Countouriotis, A. M. ;
Kantarjian, H. M. .
LEUKEMIA, 2008, 22 (06) :1200-1206