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

Abstract

A B S T R A C T PurposeFunctional 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 MethodsThis 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. ResultsThere was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb Ն12 g/dL or Hb increase Ն 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 ϭ .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 ϭ .16). ConclusionIn patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo. J Clin

A randomized comparison of once weekly epoetin alfa to extended schedule epoetin or darbepoetin in chemotherapy‐associated anemia

“…A CONSORT flow diagram is displayed in Fig. 1; 62% of enrolled patients completed all study interventions, similar to prior ESA studies in the CAA population [15,24].…”

Iron Supplementation in Nephrology and Oncology: What Do We Have in Common?

“…There was no difference in the erythropoietic response rate among the three groups. There were also no differences in the proportion of patients requiring RBC transfusion, changes in quality of life, or the dose of darbepoetin administered [46].…”

Iron Deficiency Anemia in Cancer Patients

“…58 In addition, in the study by Steensma et al, the average TSAT of patients receiving IV iron was 22.5 %. 57 This is higher than the traditional definition for functional iron deficiency in the NCCN guidelines and may perhaps explain the lack of significant response to the IV iron.…”

“…57 Patients received darbepoetin alfa once every three weeks and were randomly assigned to receive ferric gluconate (187.5 mg IV) every three weeks (n=167), oral daily ferrous sulfate (n=168), or oral placebo (n=167). No significant differences in erythropoietic response between patients receiving IV iron, oral iron, or no iron supplementation with darbepoetin alfa treatment were seen (see Figure 3), thereby calling into question the benefits of IV iron supplementation.…”

“…A recent meta-analysis of eight trials 44,[48][49][50][51][55][56][57] comparing IV iron, oral iron, or no iron when added to ESAs in anemic cancer patients found that IV iron reduces the rate of transfusions by 23 % and increases the chance of hematopoietic response by 29 % compared with ESAs alone. 53 In addition, the median time for obtaining a hematopoietic response was shortened by a month, which has both clinical and economic benefits.…”