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

Leuk Lymphoma. 2014 Sep;55(9):2114-9. doi: 10.3109/10428194.2013.867489. Epub 2014 Jan 24.

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.

Keywords: AML; Elacytarabine; clinical trial; hENT1; idarubicin; nucleoside transporter.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow / pathology
  • Cytarabine / administration & dosage
  • Cytarabine / analogs & derivatives
  • Equilibrative Nucleoside Transporter 1 / genetics
  • Equilibrative Nucleoside Transporter 1 / metabolism*
  • Female
  • Gene Expression
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Idarubicin / administration & dosage
  • Induction Chemotherapy
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Treatment Outcome
  • Young Adult

Substances

  • Equilibrative Nucleoside Transporter 1
  • Cytarabine
  • 5'-oleoyl cytarabine
  • Idarubicin