TY - JOUR
T1 - Nilotinib for the treatment of Philadelphia-chromosome-positive chronic myeloid leukemia
AU - Fullmer, Amber
AU - Kantarjian, Hagop
AU - Cortes, Jorge
AU - Jabbour, Elias
N1 - Funding Information:
H Kantarjian has received research grants from Bristol-Myers Squibb and Novartis. J Cortes has received research grants from Novartis, Bristol-Myers Squibb and Pfizer. E Jabbour has received Honoraria from Novartis and Bristol-Myers Squibb.
PY - 2010/12
Y1 - 2010/12
N2 - Importance of the field: Although the introduction of imatinib revolutionized the management of chronic myeloid leukemia (CML), some patients exhibit resistance or intolerance to the drug. Nilotinib induces high and rapid rates of cytogenetic and molecular responses. With recent approval for newly diagnosed patients with chronic phase CML, the current algorithm for treatment will probably be transformed. Areas covered in this review: This review will describe evaluations of nilotinib in all phases of CML from 1995 to the present. Early preclinical data and Phase I, Phase II and Phase III evaluations will demonstrate the role of nilotinib in newly diagnosed CML, as well as in imatinib-resistant or imatinib-intolerant disease. What the reader will gain: Mutations in the BCR-ABL kinase domain are responsible for the majority of resistance to imatinib. In comparison with imatinib, nilotinib displays increased selectivity and potency at inhibiting proliferation of BCR-ABL expressing cells. Although several mutations, including T315I, remain resistant to nilotinib, activity in all phases of CML has been reported. Take home message: Nilotinib induces high and rapid rates of cytogenetic and molecular response, with less progression to advanced forms of disease compared with imatinib. Considering that the rapid achievement of these clinical milestones has been associated with positive long-term outcomes, nilotinib as initial therapy in patients with CML in chronic phase represents the future in CML treatment. Longer follow-up is necessary to recognize survival advantages.
AB - Importance of the field: Although the introduction of imatinib revolutionized the management of chronic myeloid leukemia (CML), some patients exhibit resistance or intolerance to the drug. Nilotinib induces high and rapid rates of cytogenetic and molecular responses. With recent approval for newly diagnosed patients with chronic phase CML, the current algorithm for treatment will probably be transformed. Areas covered in this review: This review will describe evaluations of nilotinib in all phases of CML from 1995 to the present. Early preclinical data and Phase I, Phase II and Phase III evaluations will demonstrate the role of nilotinib in newly diagnosed CML, as well as in imatinib-resistant or imatinib-intolerant disease. What the reader will gain: Mutations in the BCR-ABL kinase domain are responsible for the majority of resistance to imatinib. In comparison with imatinib, nilotinib displays increased selectivity and potency at inhibiting proliferation of BCR-ABL expressing cells. Although several mutations, including T315I, remain resistant to nilotinib, activity in all phases of CML has been reported. Take home message: Nilotinib induces high and rapid rates of cytogenetic and molecular response, with less progression to advanced forms of disease compared with imatinib. Considering that the rapid achievement of these clinical milestones has been associated with positive long-term outcomes, nilotinib as initial therapy in patients with CML in chronic phase represents the future in CML treatment. Longer follow-up is necessary to recognize survival advantages.
KW - Chronic myeloid leukemia
KW - Nilotinib
KW - Tyrosine kinase inhibitor
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U2 - 10.1517/14656566.2010.535655
DO - 10.1517/14656566.2010.535655
M3 - Review article
C2 - 21073351
AN - SCOPUS:78649292029
SN - 1465-6566
VL - 11
SP - 3065
EP - 3072
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
IS - 18
ER -