Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to darbepoetin alfa for patients with chemotherapy-associated anemia

J Clin Oncol. 2011 Jan 1;29(1):97-105. doi: 10.1200/JCO.2010.30.3644. Epub 2010 Nov 22.

Abstract

Purpose: Functional iron deficiency may impair response to erythropoiesis-stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated anemia (CAA). This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA.

Patients and methods: This prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies. All patients received darbepoetin alfa once every 3 weeks and were randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV) every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks.

Results: There was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb ≥ 12 g/dL or Hb increase ≥ 2 g/dL from baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75). There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life, or the dose of darbepoetin administered. Adverse events (AEs) tended to be more common in the IV iron arm: grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46% (95% CI, 38% to 54%) who received oral placebo (P = .16).

Conclusion: In patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anemia / chemically induced
  • Anemia / drug therapy*
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Darbepoetin alfa
  • Dietary Supplements
  • Erythropoietin / administration & dosage
  • Erythropoietin / analogs & derivatives*
  • Female
  • Ferric Compounds / administration & dosage
  • Hematinics / administration & dosage*
  • Humans
  • Iron / administration & dosage*
  • Iron / adverse effects
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Prospective Studies

Substances

  • Antineoplastic Agents
  • Ferric Compounds
  • Hematinics
  • Erythropoietin
  • Darbepoetin alfa
  • Iron
  • ferric gluconate