Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival

Cancer. 2008 Dec 1;113(11):3181-5. doi: 10.1002/cncr.23927.

Abstract

Background: Acute myelogenous leukemia (AML) associated with core-binding-factor (CBF) abnormalities is the type of leukemia most responsive to cytarabine (ara-C) therapy and is of relative favorable prognosis. In vitro and ex vivo observations suggest that increases in intracellular ara-C levels influenced by administration of fludarabine and granulocyte colony-stimulating factor (GCSF) increase the effect of ara-C, prompting us to clinically evaluate the efficacy of such combinations.

Methods: We analyzed the event-free survival of patients with newly diagnosed CBF AML treated with fludarabine and ara-C (FA) (N = 45) or with FA and GCSF (FLAG) (N = 22) and compared results to patients treated with regimens consisting of idarubicin and ara-C with or without GCSF (IA/IAG) (N = 47).

Results: After accounting for prognostic covariates other than treatment (including year in which treatment was administered), FA, and in particular FLAG, were associated with longer event-free survival than IA/IAG.

Conclusions: Thus, our data lends clinical credence to the observed modulation of ara-C by fludarabine and GCSF.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Core Binding Factors / metabolism*
  • Cytarabine / therapeutic use
  • Disease-Free Survival
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Idarubicin / administration & dosage
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use

Substances

  • Core Binding Factors
  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Vidarabine
  • Idarubicin

Supplementary concepts

  • FLAG protocol