TY - JOUR
T1 - First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia
AU - Ravandi, Farhad
AU - O'Brien, Susan
AU - Thomas, Deborah
AU - Faderl, Stefan
AU - Jones, Dan
AU - Garris, Rebecca
AU - Dara, Samuel
AU - Jorgensen, Jeffrey
AU - Kebriaei, Partow
AU - Champlin, Richard
AU - Borthakur, Gautam
AU - Burger, Jan
AU - Ferrajoli, Alessandra
AU - Garcia-Manero, Guillermo
AU - Wierda, William
AU - Cortes, Jorge
AU - Kantarjian, Hagop
PY - 2010/9/23
Y1 - 2010/9/23
N2 - The combination of cytotoxic chemotherapy and imatinib has improved the outcome for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Dasatinib has significant clinical activity in patients with imatinib resistance. We examined the efficacy and safety of combining chemotherapy with dasatinib for patients with Ph+ ALL. Newly diagnosed patients received dasatinib 50 mg by mouth twice per day (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyper-CVAD, and high-dose cytarabine and methotrexate. Patients in complete remission received maintenance daily dasatinib and monthly vincristine and prednisone for 2 years, followed by dasatinib indefinitely. Thirty-five patients with untreated Ph+ ALL with a median age of 53 years (range, 21-79 years) were treated; 33 patients (94%) achieved complete remission. Two patients died of infections before response assessment. Grade 3 and 4 adverse events included hemorrhage and pleural and pericardial effusions. With a median follow-up of 14 months (range, 4-37 months), the median disease-free survival and median overall survival have not been reached, with an estimated 2-year survival of 64%. The combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph+ ALL. This study was registered at www.ClinicalTrials.gov as NCT00390793.
AB - The combination of cytotoxic chemotherapy and imatinib has improved the outcome for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Dasatinib has significant clinical activity in patients with imatinib resistance. We examined the efficacy and safety of combining chemotherapy with dasatinib for patients with Ph+ ALL. Newly diagnosed patients received dasatinib 50 mg by mouth twice per day (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyper-CVAD, and high-dose cytarabine and methotrexate. Patients in complete remission received maintenance daily dasatinib and monthly vincristine and prednisone for 2 years, followed by dasatinib indefinitely. Thirty-five patients with untreated Ph+ ALL with a median age of 53 years (range, 21-79 years) were treated; 33 patients (94%) achieved complete remission. Two patients died of infections before response assessment. Grade 3 and 4 adverse events included hemorrhage and pleural and pericardial effusions. With a median follow-up of 14 months (range, 4-37 months), the median disease-free survival and median overall survival have not been reached, with an estimated 2-year survival of 64%. The combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph+ ALL. This study was registered at www.ClinicalTrials.gov as NCT00390793.
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U2 - 10.1182/blood-2009-12-261586
DO - 10.1182/blood-2009-12-261586
M3 - Article
C2 - 20466853
AN - SCOPUS:77957191745
SN - 0006-4971
VL - 116
SP - 2070
EP - 2077
JO - Blood
JF - Blood
IS - 12
ER -