Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients

Cancer. 2012 Sep 15;118(18):4471-7. doi: 10.1002/cncr.27429. Epub 2012 Jan 26.

Abstract

Background: Standard therapy for older patients with acute myeloid leukemia (AML) has a poor outcome. The authors have designed a combination of clofarabine plus low-dose cytarabine followed by a prolonged consolidation alternating with decitabine.

Methods: Sixty patients with a median age of 70 years (range, 60-81 years) with newly diagnosed AML were included. They received clofarabine 20 mg/m(2) intravenously daily for 5 days plus cytarabine 20 mg subcutaneously twice daily for 10 days. Responding patients continued for up to 17 courses of consolidation therapy including decitabine.

Results: Forty of 59 evaluable patients responded (66%). Complete remission rate was 58%. Median relapse-free survival (RFS) was 14.1 (95% confidence interval [CI], 6.9 to not estimable), and median overall survival (OS) was 12.7 months (95% CI, 8.8 to not estimable). Median OS of responding patients (complete response [CR]/CR with platelet count <100 × 109/L) was 24.2 months (95% CI, 17 to not estimable). Compared with a historical group of patients who received clofarabine plus low-dose cytarabine with a shorter consolidation, RFS was not statistically different. Induction mortality was low (7% at 8 weeks) and toxicities manageable.

Conclusions: Clofarabine plus low-dose cytarabine alternating with decitabine in consolidation is active in older patients with newly diagnosed AML. The benefits of a prolonged consolidation remain unproven.

Publication types

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

MeSH terms

  • Adenine Nucleotides / adverse effects
  • Adenine Nucleotides / therapeutic use*
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arabinonucleosides / adverse effects
  • Arabinonucleosides / therapeutic use*
  • Azacitidine / adverse effects
  • Azacitidine / analogs & derivatives*
  • Azacitidine / therapeutic use
  • Clofarabine
  • Consolidation Chemotherapy
  • Cytarabine / adverse effects
  • Cytarabine / therapeutic use*
  • Decitabine
  • Female
  • Humans
  • Induction Chemotherapy
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Adenine Nucleotides
  • Arabinonucleosides
  • Cytarabine
  • Clofarabine
  • Decitabine
  • Azacitidine