The therapeutic landscape of chronic myeloid leukemia (CML) has changed dramatically in the last decade. In particular, the availability of imatinib mesylate, a tyrosine kinase inhibitor targeting BCR-ABL, has led to profound and durable remissions in the majority of patients. However, a couple of issues have emerged and partially obscured this scenario. First, it has become clear that a significant proportion of patients either present with primary resistance to imatinib or develop secondary resistance sooner or later during treatment. Second, although the drug is generally well tolerated, a percentage of patients eventually cease treatment because of toxicity. Bearing this in mind, second-generation tyrosine kinase inhibitors have been introduced, including nilotinib. Phase I and II studies indicate remarkable activity for this compound in CML cases resistant to imatinib, including some of those carrying BCR-ABL1 mutants. More recently, two Phase II studies and a III randomized Phase clinical trial demonstrated the superiority of nilotinib compared with imatinib in terms of complete cytogenetic and major molecular responses, which are two relevant surrogate measures of long-term survival in CML. In this paper, we review the most relevant data on nilotinib as first-line treatment for CML, and discuss the rationale for its routine use, as well as some possible future perspectives for CML patients.
Titolo: | First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation. |
Autore/i: | Pier Paolo Piccaluga; Stefania Paolini; Clara Bertuzzi; Antonio De Leo; Gianantonio Rosti |
Autore/i Unibo: | |
Anno: | 2012 |
Rivista: | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.2147/JBM.S13067 |
Abstract: | The therapeutic landscape of chronic myeloid leukemia (CML) has changed dramatically in the last decade. In particular, the availability of imatinib mesylate, a tyrosine kinase inhibitor targeting BCR-ABL, has led to profound and durable remissions in the majority of patients. However, a couple of issues have emerged and partially obscured this scenario. First, it has become clear that a significant proportion of patients either present with primary resistance to imatinib or develop secondary resistance sooner or later during treatment. Second, although the drug is generally well tolerated, a percentage of patients eventually cease treatment because of toxicity. Bearing this in mind, second-generation tyrosine kinase inhibitors have been introduced, including nilotinib. Phase I and II studies indicate remarkable activity for this compound in CML cases resistant to imatinib, including some of those carrying BCR-ABL1 mutants. More recently, two Phase II studies and a III randomized Phase clinical trial demonstrated the superiority of nilotinib compared with imatinib in terms of complete cytogenetic and major molecular responses, which are two relevant surrogate measures of long-term survival in CML. In this paper, we review the most relevant data on nilotinib as first-line treatment for CML, and discuss the rationale for its routine use, as well as some possible future perspectives for CML patients. |
Data stato definitivo: | 2018-03-30T14:03:16Z |
Appare nelle tipologie: | 1.01 Articolo in rivista |
File in questo prodotto:
File | Descrizione | Tipo | Licenza | |
---|---|---|---|---|
JBM-13067-first-line-treatment-of-chronic-myeloid-leukemia-with-niloti_112812.pdf | Versione (PDF) editoriale | Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale (CCBYNC) | Open Access Visualizza/Apri |