Hematologic Improvement and Response in Elderly AML/RAEB Patients Treated With Valproic Acid and Low-Dose Ara-C

Leuk Res. 2011 Aug;35(8):991-7. doi: 10.1016/j.leukres.2011.02.021. Epub 2011 Apr 6.

Abstract

The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has been shown to be active on acute myeloid leukemia (AML) and refractory anemia with excess of blasts (RAEB). Thirty-one elderly AML/RAEB patients (AML n=25; RAEB n=6) with a high rate of comorbidity were entered in a phase II study with low-dose cytarabine (Ara-C) and VPA. Fitness was evaluated by means of the Comprehensive Geriatric Assessment (CGA), including the Cumulative Illness Rating Scale (CIRS) score, the self-sufficiency scores of Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL). Eight patients obtained a lasting complete remission and 3 other patients obtained hematologic improvement for a total response rate of 35%. Five of 11 responding patients were relapsed or resistant after a previous treatment with Ara-C. Seven of 11 responding patients were assessed as frail at enrollment and/or had IADL impairment. Grades 3 and 4 toxicities were mainly hematological. Low-dose Ara-C and VPA is a relatively non-toxic combination with good therapeutic activity in elderly patients with AML/RAEB. This therapeutic approach represents an alternative treatment for patients who cannot undergo standard induction therapy.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia, Refractory, with Excess of Blasts / drug therapy*
  • Anemia, Refractory, with Excess of Blasts / genetics
  • Anemia, Refractory, with Excess of Blasts / pathology
  • Anticonvulsants / therapeutic use
  • Antimetabolites, Antineoplastic / therapeutic use
  • Cytarabine / therapeutic use*
  • Drug Therapy, Combination
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Remission Induction
  • Survival Rate
  • Treatment Outcome
  • Valproic Acid / therapeutic use*

Substances

  • Anticonvulsants
  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Valproic Acid