Extending the duration of response in chronic myelogenous leukemia: Targeted therapy with sequential tyrosine kinase inhibitors

Michael G. Martin, John F. Dipersio, Geoffrey L. Uy

Research output: Contribution to journalReview article

Abstract

Tyrosine kinase inhibitors (TKIs) are the mainstay for treatment of chronic myelogenous leukemia (CML). Imatinib was the first TKI approved for use in CML, but resistance to this therapy has emerged as a significant issue, and second-line options are often necessary. Increased-dose imatinib may elicit responses in some patients, but clinical evidence suggests only a minority experience sustained benefit. The second-generation TKIs, dasatinib and nilotinib, have demonstrated efficacy in patients resistant or intolerant to imatinib. Changes in therapy, with the aim of inducing durable response, should occur promptly after imatinib failure is identified as all agents are more effective in chronic phase disease than in later stages. Selection of second-line agents should be driven by efficacy and safety: dasatinib may be more effective in patients with P-loop or F359C mutations; nilotinib may be more effective in those with F317L mutations.

Original languageEnglish
Pages (from-to)59-70
Number of pages12
JournalOncology Reviews
Volume3
Issue number1
DOIs
StatePublished - Feb 24 2009

Keywords

  • BCR-ABL
  • CML
  • Dasatinib
  • Imatinib
  • Nilotinib
  • Philadelphia chromosome

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