title: A phase II study of elacytarabine in combination with idarubicin and of human equilibrative nucleoside transporter 1 expression in patients with acute myeloid leukemia and persistent blasts after the first induction course.
abstract: Unlike cytarabine, cellular entry of Elacytarabine, the elaidic acid ester derivative of cytarabine, is independent of the human equilibrative nucleoside transporter 1 (hENT1). This phase II study tested whether the hENT1 blast expression level can be used as a predictive marker for cytarabine response and if the efficacy of elacytarabine is independent of hENT1 expression. A total of 51 patients with acute myeloid leukemia (AML) induction failure were given elacytarabine-idarubicin as a second induction course. The hENT1 expression level was analyzed prior to first induction and/or prior to treatment with elacytarabine. The overall response rate (ORR) was 41% and the safety profile was manageable. There is a trend suggesting that hENT1 expression influences response to cytarabine, but not sufficient to support it as a biomarker for guiding treatment. Further, we conclude that the activity of elacytarabine is not significantly predicted by the hENT1 expression level.
authors.affiliation: Duke University Medical Center , Durham, NC , USA.
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Françoise
authors.initials: F
authors.lastname: Huguet-Rigal
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Thomas
authors.initials: T
authors.lastname: Kindler
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Igor Wolfgang
authors.initials: IW
authors.lastname: Blau
authors.forename: Tove Flem
authors.initials: TF
authors.lastname: Jacobsen
authors.forename: Malin
authors.initials: M
authors.lastname: Johansen
authors.forename: Trygve
authors.initials: T
authors.lastname: Bergeland
authors.forename: Athos
authors.initials: A
authors.lastname: Gianella-Borradori
authors.forename: Utz
authors.initials: U
authors.lastname: Krug
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D003561:Cytarabine; C047645:5'-oleoyl cytarabine; D015255:Idarubicin
keywords: AML; Elacytarabine; clinical trial; hENT1; idarubicin; nucleoside transporter