Intravenous (IV) Iron Supplementation in Patients with Chemotherapy-Induced Anemia (CIA) Receiving Darbepoetin alfa Every 3 Weeks (Q3W): Iron Parameters in a Randomized Controlled Trial.

Abstract

Background and Aim: The role of IV iron supplementation during treatment with erythropoiesis-stimulating agents (ESAs) in patients with CIA is of increasing interest as a possible means of improving response. This randomized, open-label, multicenter study was designed to evaluate the safety and efficacy of IV iron vs standard practice in CIA patients receiving darbepoetin alfa. Interim efficacy analyses showed a higher response rate for darbepoetin alfa with IV iron compared to darbepoetin alfa with standard iron practice with no difference in the safety profile between the treatment arms (Vanderbroek et al, EHA 2006). Iron parameters are reported here. Methods: Eligible patients were diagnosed with a non-myeloid malignancy and had CIA with a baseline hemoglobin (Hb) value < 11g/dL. All patients received darbepoetin alfa 500 mcg administered Q3W with the SureClick™ prefilled autoinjector. Patients were randomized 1:1 to IV iron 200 mg (single dose Q3W at the same time as darbepoetin alfa or in 2 doses of 100 mg within 3 weeks) or standard practice (oral iron or no iron). Randomization was stratified by tumor type and baseline Hb category (< 10 or ≥10 g/dL). Results: A total of 400 patients were randomized. Mean (SD) age of the study population was 61.4 (11.5) years; range, 20–86. Sixty percent (n=241) of participants were women; 28% (n=114) had lung or gynecological tumors; and 52% (n=208) had a baseline Hb value ≥10 g/dL. In the interim analysis population (n=196), the mean (SD) weekly dose of IV iron was 64.8 (6.6) mg in the IV iron group (n=100). In the standard practice group, 28 of 96 patients (29%) received oral iron and 2 (2%) received IV iron (these patients were analyzed as randomized). Mean (standard error) serum ferritin concentrations and percent transferrin saturation (TSAT) in the 2 groups from baseline (BL) to end of study (EOS) are shown in the figure. Conclusions: The combination of darbepoetin alfa Q3W and IV iron appeared to be associated with a trend toward increased mean serum ferritin levels compared to the standard practice control arm. In contrast, mean TSAT surprisingly appeared to be similar in the 2 groups for most of the study period, perhaps suggesting that TSAT is influenced by other factors. Iron management appears to be an important factor in the response to ESAs and the findings presented here suggest the need for additional exploration into iron uptake and demand in cancer patients treated with darbepoetin alfa. Serum Ferritin Concentration Serum Ferritin Concentration Transferrin Saturation (%) Transferrin Saturation (%)

Roles of Intravenous Iron Therapy in Various Patient Settings

“…As discussed previously, the benefits of iron supplementation during ESA therapy have been well established in chemotherapy-induced anemia, even in patients with TSAT levels of 20-35% and sFerr levels of 100-900 ng/mL. [33][34][35][36][37][38][39] Furthermore, recent pharmacoeconomic analysis demonstrated significantly improved cost-effectiveness of ESA therapy when used in conjunction with intravenous iron; the addition of intravenous iron resulted in a cost saving of $1300 per 12-week treatment cycle per patient. 1 Multiple studies have indicated that intravenous iron supplementation enhances ESA therapy in patients with chemotherapy-induced anemia whose TSAT levels are <35% and sFerr levels are 100-900 ng/mL.…”

“…22,23, 25 Hepcidin interferes with enteral iron absorption and promotes iron degradation; the mechanism by which hepcidin promotes the degradation of iron is interference with both the iron release from macrophages and iron transport by ferroportin. Table 2 4,33-41 and Table 3 4, [33][34][35][36][37][38][39][40][41][42][43][44] summarize factors that need to be considered when assessing for iron deficiency and specific indicators for iron deficiency, respectively.…”

“…1 Multiple studies have indicated that intravenous iron supplementation enhances ESA therapy in patients with chemotherapy-induced anemia whose TSAT levels are <35% and sFerr levels are 100-900 ng/mL. [33][34][35][36][37][38][39] This evidence-based treatment approach will benefit patients with cancer by improving their overall treatment outcome (reduce the requirement for blood transfusions and decrease the risk of thromboembolic events) and improve cost-effectiveness of ESA therapy in oncology settings.…”

The use of intravenous iron in patients with cancer‐related anaemia

“…Finally, three studies have been reported so far in abstract form only. The first was a trial of 400 cancer patients with chemotherapy‐induced anaemia treated with darbepoetin in which patients were randomised to intravenous iron (Venofer ® ) or standard care (29% of whom received oral iron) (Lerchenmueller et al , 2006; Vandebroek et al , 2006). An interim analysis suggests an improved haemoglobin response in the intravenous iron group.…”

Clinical experience with intravenous iron

“…However, longer‐acting ESAs have been developed. One study 39 showed a statistically significant increment in hemoglobin levels and a decrease in transfusion requirements in patients receiving darbepoetin alfa every 3 weeks plus intravenous ferric gluconate or iron sucrose. These data were not stratified for baseline iron parameters.…”