Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy - PubMed (original) (raw)
Clinical Trial
. 2007 Mar 15;109(6):2303-9.
doi: 10.1182/blood-2006-09-047266. Epub 2006 Nov 30.
Hagop M Kantarjian, Michele Baccarani, Jeffrey H Lipton, Jane F Apperley, Brian J Druker, Thierry Facon, Stuart L Goldberg, Francisco Cervantes, Dietger Niederwieser, Richard T Silver, Richard M Stone, Timothy P Hughes, Martin C Muller, Rana Ezzeddine, Athena M Countouriotis, Neil P Shah
Affiliations
- PMID: 17138817
- DOI: 10.1182/blood-2006-09-047266
Free article
Clinical Trial
Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy
Andreas Hochhaus et al. Blood. 2007.
Free article
Erratum in
- Blood. 2007 Sep 1;110(5):1438
Abstract
Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.
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