title: Elacytarabine in relapsed/refractory acute myeloid leukaemia: an evaluation of clinical efficacy, pharmacokinetics, cardiac safety and effects on lipid profile.
abstract: Elacytarabine is the elaidic acid ester derivative of cytarabine, designed to enter cells independently of nucleoside transporters. Effects of elacytarabine on QT interval, serum lipid profile and clinical activity were investigated in 43 relapsed/refractory AML patients. Mean maximum increase in corrected QT interval of 24( ± 29)ms occurred 48 h after elacytarabine infusion without associated arrhythmias or clinical symptoms. A non-clinically significant, elacytarabine exposure-dependent increase in cholesterol was caused by a cholesterol rich lipoprotein depleted of apolipoprotein B formed by infused phospholipids complexing cholesterol. Elacytarabine is clinically active in relapsed/refractory AML: overall response rate (CR + CRi) was 44% (16/36 with 7 non-evaluable patients) and adverse events were manageable. Clinical Trials.gov Identifier: NCT01258816.
authors.affiliation: Department of Haematology, Cardiff University, Cardiff, UK. Electronic address: knappers@cardiff.ac.uk.
authors.forename: Steven
authors.initials: S
authors.lastname: Knapper
authors.affiliation: Royal Sussex County Hospital, Brighton, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Chevassut
authors.affiliation: Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Duarte
authors.affiliation: Hospital San Pedro de Alcántara, Cáceres, Spain.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Bergua
authors.affiliation: Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Salamero
authors.affiliation: Clavis Pharma ASA, Oslo, Norway.
authors.forename: Malin
authors.initials: M
authors.lastname: Johansen
authors.affiliation: Clavis Pharma ASA, Oslo, Norway.
authors.forename: Tove Flem
authors.initials: TF
authors.lastname: Jacobsen
authors.affiliation: Clavis Pharma ASA, Oslo, Norway.
authors.forename: Petter-Arnt
authors.initials: PA
authors.lastname: Hals
authors.affiliation: Clavis Pharma ASA, Oslo, Norway.
authors.forename: Wenche
authors.initials: W
authors.lastname: Rasch
authors.affiliation: Clavis Pharma ASA, Oslo, Norway.
authors.forename: Athos
authors.initials: A
authors.lastname: Gianella-Borradori
authors.affiliation: St Bartholomew's Hospital, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008074:Lipoproteins; D003561:Cytarabine; C047645:5'-oleoyl cytarabine; D002784:Cholesterol
keywords: AML; Cardiac safety; Cholesterol; ECG; Elacytarabine; Lipoprotein; QT