Optimizing treatment with Bcr-Abl tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia: Focus on dosing schedules

Elias Jabbour, Jorge E. Cortés, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome (Ph), a genetic aberration that codes for bcr-abl, which plays a key role in disease pathophysiology. The first oral inhibitor of Brc-Abl was imatinib, which also targets KIT and platelet-derived growth factor receptor kinase and has demonstrated improved outcomes when compared with interferon, the previous standard of care. Imatinib resistance and intolerance have been an issue for patients, and as a result, new therapeutic approaches have been evaluated. Dose-escalated imatinib (800 mg daily) has shown some limited activity in patients with imatinib-resistant CML, but the development of second-generation tyrosine kinase inhibitors has broadened the treatment options. Dasatinib is also an oral kinase inhibitor, but it has increased potency for Brc-Abl compared with imatinib. Dasatinib has demonstrated activity in all phases of CML and Ph+ acute lymphocytic leukemia and is approved for the treatment of adults in this setting. Recent phase III data have demonstrated that, in patients with chronic-phase CML, dasatinib 100 mg once daily is equally effective, with improved tolerability, compared with the previously approved 70-mg twice-daily dose. Nilotinib, which has been recently approved, has increased potency for Brc-Abl compared with imatinib and has demonstrated activity in patients with imatinib-resistant and -intolerant chronic- and accelerated-phase CML. As experience with these agents continues to mature, we might optimize the treatment efficacy and safety profiles by altering dose regimens.

Original languageEnglish (US)
Pages (from-to)S75-S81
JournalClinical Lymphoma and Myeloma
Volume8
Issue numberSUPPL. 3
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

bcr-abl Fusion Proteins
Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Appointments and Schedules
Leukemia, Myeloid, Chronic Phase
Therapeutics
Leukemia, Myeloid, Accelerated Phase
Phosphotransferases
Genetic Code
Platelet-Derived Growth Factor Receptors
Standard of Care
Imatinib Mesylate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Protein-Tyrosine Kinases
Interferons
Safety

Keywords

  • Dasatinib
  • Dose optimization
  • Imatinib
  • Nilotinib

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Optimizing treatment with Bcr-Abl tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia : Focus on dosing schedules. / Jabbour, Elias; Cortés, Jorge E.; Kantarjian, Hagop.

In: Clinical Lymphoma and Myeloma, Vol. 8, No. SUPPL. 3, 03.2008, p. S75-S81.

Research output: Contribution to journalArticle

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