title: Safety and clinical activity of 5-aza-2'-deoxycytidine (decitabine) with or without Hyper-CVAD in relapsed/refractory acute lymphocytic leukaemia.
abstract: To test the safety and activity of 5-aza-2'-deoxycytidine (decitabine) in patients with relapsed/refractory acute lymphocytic leukaemia (ALL), we conducted a phase 1 study with two parts: administering decitabine alone or in combination with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine). Patients participated in either part of the study or in both parts sequentially. In the initial part, decitabine was administered intravenously at doses of 10-120 mg/m(2) per d for 5 d every other week in cycles of 28 d. In the combination part, patients were treated on the first 5 d of Hyper-CVAD with intravenous decitabine at 5-60 mg/m(2) per d. A total of 39 patients received treatment in the study: 14 in the first part only, 16 sequentially in both parts and 9 in the second part only. Decitabine was tolerated at all doses administered, and grade 3 or 4 toxic effects included non-life-threatening hepatotoxicity and hyperglycaemia. Induction of DNA hypomethylation was observed at doses of decitabine up to 80 mg/m(2) . Some patients who had previously progressed on Hyper-CVAD alone achieved a complete response when decitabine was added. Decitabine alone or given with Hyper-CVAD is safe and has clinical activity in patients with advanced ALL.
authors: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Christopher B
authors: CB
authors: Benton
authors: Deborah A
authors: DA
authors: Thomas
authors: Hui
authors: H
authors: Yang
authors: Farhad
authors: F
authors: Ravandi
authors: Michael
authors: M
authors: Rytting
authors: Susan
authors: S
authors: O'Brien
authors: Anna R
authors: AR
authors: Franklin
authors: Gautam
authors: G
authors: Borthakur
authors: Samuel
authors: S
authors: Dara
authors: Monica
authors: M
authors: Kwari
authors: Sherry R
authors: SR
authors: Pierce
authors: Elias
authors: E
authors: Jabbour
authors: Hagop
authors: H
authors: Kantarjian
authors: Guillermo
authors: G
authors: Garcia-Manero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000737:chemistry; D000077209:Decitabine; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D003561:Cytarabine; D014750:Vincristine; D000077209:Decitabine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D001374:Azacitidine; D008727:Methotrexate
keywords: DNA methylation; clinical trial; decitabine; precursor cell lymphoblastic leukaemia-Lymphoma