Beyond dose escalation: Clinical options for relapse or resistance in chronic myelogenous leukemia

Jorge Cortes, Hagop Kantarjian

Research output: Contribution to journalReview article

Abstract

The development of imatinib has changed the management of chronic myeloid leukemia (CML), producing high response rates in most patients. However, most individuals treated with imatinib, 400 mg, have residual molecular disease, and both intrinsic and acquired resistance can occur. The newer tyrosine kinase inhibitors, dasatinib and nilotinib, are effective in patients with imatinib-resistant CML. In patients with relapse or resistance, current guidelines recommend escalating the dose of imatinib or switching to new tyrosine kinase inhibitors. Dasatinib has been investigated in patients who were resistant or intolerant to imatinib. Switching to dasatinib, 70 mg, twice daily has been shown to be more effective than high-dose imatinib. Another study found that dasatinib, 100 mg, once daily was just as effective as the twice-daily regimen but was better tolerated. Nilotinib is also effective in most patients with resistance or intolerance to imatinib and is associated with minimal toxicity. Other inhibitors, such as bosutinib and INNO-406, are being developed with favorable early results. New drugs are still needed, particularly for individuals who are resistant to tyrosine kinase inhibitors or those with the T315I mutation. Emerging CML therapies, some of which have different mechanisms of action from those of tyrosine kinase inhibitors, have shown promising results and could offer an alternative to these patients as monotherapy or in combination.

Original languageEnglish (US)
Pages (from-to)S22-S30
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume6
Issue numberSUPPL. 2
StatePublished - Jun 30 2008
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Recurrence
Protein-Tyrosine Kinases
Imatinib Mesylate
Guidelines
Mutation
Dasatinib
Pharmaceutical Preparations

Keywords

  • BCR-ABL
  • Chronic myeloid leukemia
  • Dasatinib
  • Imatinib
  • Nilotinib
  • Tyrosine kinase

ASJC Scopus subject areas

  • Oncology

Cite this

Beyond dose escalation : Clinical options for relapse or resistance in chronic myelogenous leukemia. / Cortes, Jorge; Kantarjian, Hagop.

In: JNCCN Journal of the National Comprehensive Cancer Network, Vol. 6, No. SUPPL. 2, 30.06.2008, p. S22-S30.

Research output: Contribution to journalReview article

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