TY - JOUR
T1 - Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure
T2 - The START a trial
AU - Apperley, Jane F.
AU - Cortes, Jorge E.
AU - Kim, Dong Wook
AU - Roy, Lydia
AU - Roboz, Gail J.
AU - Rosti, Gianantonio
AU - Bullorsky, Eduardo O.
AU - Abruzzese, Elisabetta
AU - Hochhaus, Andreas
AU - Heim, Dominik
AU - De Souza, Carmino A.
AU - Larson, Richard A.
AU - Lipton, Jeffrey H.
AU - Khoury, H. Jean
AU - Kim, Hyeoung Joon
AU - Sillaber, Christian
AU - Hughes, Timothy P.
AU - Erben, Philipp
AU - Van Tornout, Jan
AU - Stone, Richard M.
PY - 2009/7/20
Y1 - 2009/7/20
N2 - Purpose: 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. Patients and Methods: Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results: 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%). Conclusion: Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
AB - Purpose: 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. Patients and Methods: Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results: 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%). Conclusion: Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
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U2 - 10.1200/JCO.2007.14.3339
DO - 10.1200/JCO.2007.14.3339
M3 - Article
C2 - 19487385
AN - SCOPUS:70249141675
SN - 0732-183X
VL - 27
SP - 3472
EP - 3479
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 21
ER -