Abstract
Tyrosine kinase inhibitor therapy has revolutionized the outcome of chronic myeloid leukemia (CML), and has transformed a fatal disease into a chronic condition for most patients. At present, the therapeutic armamentarium against CML includes imatinib for newly diagnosed patients, and dasatinib and nilotinib, which have both received marketing approval, for imatinib-resistant and imatinib-intolerant disease. Research efforts are now focused on how to optimize therapeutic strategies in an attempt to improve clinical results further, counteract the development of drug resistance and reduce adverse effects. A randomized, international, phase III study of dasatinib dose and schedule optimization in imatinib-resistant and imatinib-intolerant patients with CML has demonstrated that intermittent target inhibition can preserve therapeutic efficacy and reduce toxicity. This finding has important implications, not only for patients with CML, but also for the development of targeted therapies for human malignancies in general.
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References
Druker B et al. (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355: 2408–2417
Talpaz M et al. (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354: 2531–2541
Hochhaus A et al. (2007) Dasatinib induces notable hematologic and cytogenetic responses in chronic phase chronic myeloid leukemia after failure of imatinib therapy. Blood 109: 2307–2309
Guilhot F et al. (2007) Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood 109: 4143–4150
Cortes J et al. (2007) Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 109: 3207–3213
Shah N et al. (2008) Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 26: 3204–3212
Soverini S et al. (2007) Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. Haematologica 92: 401–404
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G Martinelli is on the Speakers bureau for Bristol-Myers Squibb. Simona Soverini, Ilaria Iacobucci and Michele Baccarani declared no competing interests.
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Martinelli, G., Soverini, S., Iacobucci, I. et al. Intermittent targeting as a tool to minimize toxicity of tyrosine kinase inhibitor therapy. Nat Rev Clin Oncol 6, 68–69 (2009). https://doi.org/10.1038/ncponc1276
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DOI: https://doi.org/10.1038/ncponc1276
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