title: 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.
abstract: 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.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. fravandi@mdanderson.org
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Rebecca
authors.initials: R
authors.lastname: Garris
authors.forename: Samuel
authors.initials: S
authors.lastname: Dara
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jorgensen
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D000069439:Dasatinib; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011743:Pyrimidines / Q000008:administration & dosage* / Q000627:therapeutic use; D012074:Remission Induction; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D011743:Pyrimidines; D013844:Thiazoles; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069439:Dasatinib
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