Dr. Cortes report

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J Natl Compr Canc Netw. 2008 Mar;6 Suppl 2:S22-S30.

Beyond dose escalation: clinical options for relapse or resistance in

chronic myelogenous leukemia.

Cortes J, Kantarjian H. The University of Texas M. D. Cancer Center,

Houston, Texas 77030, USA. jcortes@...

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

T3151 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. PMID: 18397678 [PubMed - in process]