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RISS 인기검색어
- 검색키워드
- 저자 : Bullorsky, Eduardo O. (검색결과 2 건)
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Guilhot, Francois,Apperley, Jane,Kim, Dong-Wook,Bullorsky, Eduardo O.,Baccarani, Michele,Roboz, Gail J.,Amadori, Sergio,de Souza, Carmino A.,Lipton, Jeffrey H.,Hochhaus, Andreas,Heim, Dominik,Larson, American Society of Hematology 2007 Blood Vol.109 No.10
<B>Abstract</B><P>Treatment options are limited for patients with imatinib-resistant or -intolerant accelerated phase chronic myeloid leukemia (CML-AP). Dasatinib is a novel, potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC-family kinases that showed marked efficacy in a phase 1 trial of patients with imatinib-resistant CML. Results are presented for 107 patients with CML-AP with imatinib-resistance or -intolerance from a phase 2, open-label study further evaluating dasatinib efficacy and safety. At 8 months' minimum follow-up, 81%, 64%, and 39% of patients achieved overall, major (MaHR), and complete hematologic responses, respectively, whereas 33% and 24% attained major and complete cytogenetic remission. Of 69 patients who achieved MaHR, 7 progressed. Seventy-six percent of patients are estimated to be alive and progression-free at 10 months. Response rates for the 60% of patients with baseline BCR-ABL mutations did not differ from the total population. Dasatinib was well tolerated: most nonhematologic adverse events (AEs) were mild to moderate; no imatinib-intolerant patients discontinued dasatinib because of AEs. Although common (76% of patients with severe neutropenia), cytopenias were manageable through dose modification. In summary, dasatinib induced significant hematologic and cytogenetic responses in patients with imatinib resistance or intolerance, was well tolerated, and may represent a potent new therapeutic option for CML-AP. Further follow-up is warranted. This trial was registered at www.clinicaltrials.gov as #CA180005.</P>
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Apperley, Jane F.,Cortes, Jorge E.,Kim, Dong-Wook,Roy, Lydia,Roboz, Gail J.,Rosti, Gianantonio,Bullorsky, Eduardo O.,Abruzzese, Elisabetta,Hochhaus, Andreas,Heim, Dominik,de Souza, Carmino A.,Larson, American Society of Clinical Oncology 2009 Journal of clinical oncology Vol.27 No.21
<B>Purpose</B><P>Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population.</P><B>Patients and Methods</B><P>Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily.</P><B>Results</B><P>At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%).</P><B>Conclusion</B><P>Dasatinib is effective in patients with CML-AP after imatinib treatment failure.</P>
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