Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia

Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia

Radhakrishnan Ramchandren, Charles A SchifferDivision of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USAAbstract: The development of imatinib for the treatment of chronic myeloid leukemia (CML) has proven to be an example of medical success...

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Autores principales: Radhakrishnan Ramchandren, Charles A Schiffer
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2009
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/22a41d57922f409f808697601d0692bd
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spelling oai:doaj.org-article:22a41d57922f409f808697601d0692bd2021-12-02T08:09:14ZDasatinib in the treatment of imatinib refractory chronic myeloid leukemia1177-54751177-5491https://doaj.org/article/22a41d57922f409f808697601d0692bd2009-05-01T00:00:00Zhttp://www.dovepress.com/dasatinib-in-the-treatment-of-imatinib-refractory-chronic-myeloid-leuk-a3112https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Radhakrishnan Ramchandren, Charles A SchifferDivision of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USAAbstract: The development of imatinib for the treatment of chronic myeloid leukemia (CML) has proven to be an example of medical success in the era of targeted therapy. However, imatinib resistance or intolerance occurs in a substantial number of patients. Additionally, patients who have progressed beyond the chronic phase of CML do relatively poorly with imatinib therapy. Mechanisms of imatinib resistance include BCR-ABL point mutations resulting in decreased imatinib binding, as well as mutation-independent causes of resistance such as SRC family kinase dysregulation, BCR-ABL gene amplification, drug influx/efflux mechanisms and other poorly understood processes. The options for therapy in these patients include stem cell transplantation, imatinib dose escalation as well as the use of second-generation tyrosine kinase inhibitors. Dasatinib is a second-generation multi-kinase inhibitor with several theoretical and mechanistic advantages over imatinib. Moreover, several studies have evaluated dasatinib in patients who have progressed on imatinib therapy with encouraging results. Other novel agents such as mTOR inhibitors, bosutinib and INNO 406 have also shown promise in this setting. Although treatment options have increased, the choice of second-line therapy in patients with CML is influenced by concerns surrounding the duration of response as well as toxicity. Consequently, there is no agreed upon optimal second-line agent. This paper reviews the current data and attempts to address these issues. Keywords: chronic myeloid leukemia (CML), dasatinib, imatinib, resistance (imatinib resistance), nilotinib, tyrosine kinase inhibitor Radhakrishnan RamchandrenCharles A SchifferDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2009, Iss default, Pp 205-214 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Radhakrishnan Ramchandren
Charles A Schiffer
Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
description Radhakrishnan Ramchandren, Charles A SchifferDivision of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USAAbstract: The development of imatinib for the treatment of chronic myeloid leukemia (CML) has proven to be an example of medical success in the era of targeted therapy. However, imatinib resistance or intolerance occurs in a substantial number of patients. Additionally, patients who have progressed beyond the chronic phase of CML do relatively poorly with imatinib therapy. Mechanisms of imatinib resistance include BCR-ABL point mutations resulting in decreased imatinib binding, as well as mutation-independent causes of resistance such as SRC family kinase dysregulation, BCR-ABL gene amplification, drug influx/efflux mechanisms and other poorly understood processes. The options for therapy in these patients include stem cell transplantation, imatinib dose escalation as well as the use of second-generation tyrosine kinase inhibitors. Dasatinib is a second-generation multi-kinase inhibitor with several theoretical and mechanistic advantages over imatinib. Moreover, several studies have evaluated dasatinib in patients who have progressed on imatinib therapy with encouraging results. Other novel agents such as mTOR inhibitors, bosutinib and INNO 406 have also shown promise in this setting. Although treatment options have increased, the choice of second-line therapy in patients with CML is influenced by concerns surrounding the duration of response as well as toxicity. Consequently, there is no agreed upon optimal second-line agent. This paper reviews the current data and attempts to address these issues. Keywords: chronic myeloid leukemia (CML), dasatinib, imatinib, resistance (imatinib resistance), nilotinib, tyrosine kinase inhibitor
format article
author Radhakrishnan Ramchandren
Charles A Schiffer
author_facet Radhakrishnan Ramchandren
Charles A Schiffer
author_sort Radhakrishnan Ramchandren
title Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_short Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_full Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_fullStr Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_full_unstemmed Dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
title_sort dasatinib in the treatment of imatinib refractory chronic myeloid leukemia
publisher Dove Medical Press
publishDate 2009
url https://doaj.org/article/22a41d57922f409f808697601d0692bd
work_keys_str_mv AT radhakrishnanramchandren dasatinibinthetreatmentofimatinibrefractorychronicmyeloidleukemia
AT charlesaschiffer dasatinibinthetreatmentofimatinibrefractorychronicmyeloidleukemia
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