Intravenous Iron Optimizes the Response to Recombinant Human Erythropoietin in Cancer Patients With Chemotherapy-Related Anemia: A Multicenter, Open-Label, Randomized Trial

2004 ◽  
Vol 22 (7) ◽  
pp. 1301-1307 ◽  
Author(s):  
Michael Auerbach ◽  
Harold Ballard ◽  
J. Richard Trout ◽  
Marilyn McIlwain ◽  
Alan Ackerman ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Cancer Patients ◽  
Recombinant Human Erythropoietin ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Iron Dextran ◽  
Iron Group ◽  
Open Label ◽  
Human Erythropoietin ◽  
Iv Iron

PurposeRecombinant human erythropoietin (rHuEPO) is the standard of care for patients with chemotherapy-related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response and decreases dosage requirements in patients with anemia of kidney disease, but its effect has not been studied in randomized trials in cancer patients.MethodsThis prospective, multicenter, open-label, randomized trial enrolled 157 patients with chemotherapy-related anemia (Hb ≤ 105 g/L, serum ferritin ≤ 450 pmol/L or ≤ 675 pmol/L with transferrin saturation ≤ 19%) receiving subcutaneously rHuEPO 40,000 U once weekly to: (1) no-iron; (2) oral iron 325 mg twice daily; (3) iron dextran repeated 100mg IV bolus; or (4) iron dextran total dose infusion (TDI). Hb and quality of life (QOL) were measured at baseline and throughout.ResultsAll groups showed Hb (P < .0001) increases from baseline. Mean Hb increases for both IV iron groups were greater (P < .02) than for no-iron and oral iron groups. The percentage of patients with hematopoietic responses was higher (P < .01) in both IV iron groups (each case 68%) compared with no-iron (25%) and oral iron (36%) groups. IV iron groups showed increases in energy, activity, and overall QOL from baseline, compared with a decrease in energy and activity for no-iron group and no change in activity or overall QOL for oral iron group.ConclusionrHuEPO increases Hb levels and improves QOL in patients with chemotherapy-related anemia. Magnitude of Hb increase and QOL improvement is significantly greater if IV iron is added.

scholarly journals Baseline Hepcidin Does Not Predict the Response to Iron Therapy in Pregnant Women with Iron Deficiency

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3076-3076
Author(s):  
Rebecka Hansen ◽  
Joergen Kurtzhals ◽  
Bjarne Styrishave ◽  
Charlotte Holm
Keyword(s):  
Iron Deficiency ◽  
Pregnant Women ◽  
Conflicts Of Interest ◽  
Controlled Trial ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Iron Group ◽  
Open Label

Abstract Introduction: Hepcidin, the master regulator of iron economy, is decreased during pregnancy to facilitate adequate iron transfer across the placenta. Conversely, iron need increases substantially during pregnancy often leading to iron deficiency and subsequently anemia. The PREG-01 Study compared the efficacy and safety of intravenous (IV) ferric derisomaltose (FDI) vs. oral iron in treating persistent iron deficiency in pregnant women. The study found FDI to be efficacious and well-tolerated in pregnancy and the proportion of non-anaemic patients throughout the course of the study was significantly lower in the FDI group. In this analysis, we investigated the effect of baseline hepcidin on the response to IV and oral iron therapy. Methods: PREG-01 was a single-centre, open-label, randomized controlled trial. Women 14-21 weeks pregnant with persistent iron deficiency (ferritin&lt;30 µg/L despite oral iron treatment) received a single intravenous 1000 mg dose of FDI (n=100) or 100 mg elemental oral iron daily combined with ascorbic acid (n=101). Hemoglobin (Hb), ferritin and transferrin saturation (TSAT%) levels were captured at baseline and monitored throughout the study. The effect of baseline hepcidin on achieving non-anemic status (Hb ≥ 11 g/dL) at all study visits and the effect on change in Hb, ferritin and TSAT% were investigated by estimating odds ratios from a logistic regression model with treatment as factor and interaction between treatment and baseline hepcidin. The odds ratio estimate is for an increment in baseline hepcidin of 1 ng/mL. Results: Mean [standard deviation (SD)] baseline Hb was 11.97 (0.93) g/dL in the FDI group and 11.75 (0.91) g/dL in the oral iron group. Baseline hepcidin was 6.42 ng/mL in the FDI and 5.32 ng/mL in the oral iron group. Baseline hepcidin was not associated with the ability to achieve non-anaemic status either in the FDI (OR 0.98; 95% CI: 0.87-1.09) or the oral iron group (OR 0.96; 95% CI: 0.88-1.05). No statistically significant associations were found between baseline hepcidin and change in Hb, ferritin or TSAT% throughout the study (Figure 1). Conclusions: In a population of pregnant women with iron deficiency, but otherwise healthy, baseline hepcidin was overall low. Although there was a trend for an association between baseline hepcidin and Hb response to oral iron only, baseline hepcidin did not predict the response to iron therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Ferric Derisomaltose is an IV iron preparation indicated for the treatment of iron deficiency anemia in the US.

scholarly journals Intravenous infusion of total dose iron is superior to oral iron in treatment of anemia in peritoneal dialysis patients: a single center comparative study.

1998 ◽  
Vol 9 (4) ◽  
pp. 664-668 ◽  
Author(s):  
N Ahsan
Keyword(s):  
Peritoneal Dialysis ◽  
Total Dose ◽  
Intravenous Infusion ◽  
Iron Supplementation ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Outpatient Setting ◽  
Oral Iron ◽  
Human Erythropoietin ◽  
Oral Group

In the treatment of anemia of chronic renal failure, the most common cause of recombinant human erythropoietin (rhEPO) resistance is iron deficiency. In peritoneal dialysis (PD) patients, oral iron therapy is an accepted and convenient method of iron supplementation. The effectiveness of oral iron, however, is limited by many factors, including gastrointestinal side effects and poor gastric absorption. This study prospectively compared the efficacy of single intravenous infusion of total dose iron (ITDI group) given in an outpatient setting with oral iron (oral group) for the treatment of anemia in PD patients. Twenty-five adult stable PD patients with baseline hematocrit 25 to 35% were entered into the study. Thirteen patients with serum transferrin saturation (TSAT) < 25% received ITDI, and 12 patients with TSAT between 25 and 35% received oral iron. One patient in the oral group received emergent blood transfusion and was excluded from analysis. Hematocrit and iron indices were measured at monthly intervals. Doses of rhEPO were adjusted monthly to maintain target hematocrit at 35%. At the end of the study (6 mo), despite similar baseline mean hematocrit (31.0 +/- 0.9 versus 33.0 +/- 1.0%), comparable mean baseline weekly rhEPO dose (7886 +/- 1449 versus 6370 +/- 1553 U/wk), and significantly lower level of mean TSAT (11.3 +/- 3.5 versus 30.1 +/- 3.5%; P < 0.05), the ITDI group when compared with the oral group had significantly higher mean hematocrit (36.0 +/- 1.0 versus 31.4 +/- 1.1%; P < 0.05) and TSAT (33.7 +/- 3.7 versus 22.6 +/- 4.0%; P < 0.05) values. In addition, the final mean dose of weekly rhEPO was significantly lower in the ITDI group (4799 +/- 981 versus 9998 +/- 1027 U/wk; P < 0.05). No patient in the ITDI group developed an adverse reaction to intravenous iron. It is concluded that ITDI represents a more efficacious method of iron supplementation in PD patients receiving rhEPO. Moreover, ITDI is safe and well tolerated and can be administered in an outpatient setting.

Hepatic computed tomography for monitoring the iron status of haemodialysis patients with haemosiderosis treated with recombinant human erythropoietin

1991 ◽  
Vol 81 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Sergio De Marchi ◽  
Emanuela Cecchin
Keyword(s):  
Computed Tomography ◽  
Serum Ferritin ◽  
Recombinant Human Erythropoietin ◽  
Chelation Therapy ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Ferritin Concentration ◽  
Human Erythropoietin ◽  
Serum Ferritin Concentration ◽  
Erythropoietin Treatment

1. A randomized, partial-crossover study was conducted in uraemic patients with dialysis-associated anaemia and transfusional iron overload to evaluate the effects of desferrioxamine chelation therapy and of recombinant human erythropoietin treatment on hepatic iron storage determined by computed tomography, as well as by serum ferritin concentration and transferrin saturation. 2. Twenty-one haemodialysis patients with moderate iron overload, confirmed by values of serum ferritin concentration, transferrin saturation and hepatic computed tomography density exceeding 1000 μg/l, 45% and 68 Hounsfield units respectively, were randomly allocated to three groups and were followed for 12 months. 3. During the first 6 months group 1 (n = 7) received desferrioxamine chelation therapy (30 mg/kg intravenously three times a week) and group 2 (n = 7) underwent recombinant human erythropoietin treatment (36 units/kg intravenously three times a week). Thereafter, in the second 6 months of observation patients in group 1 were switched to receive recombinant human erythropoietin. Because of a poor response in the desferrioxaminetreated group in the initial 6 months, patients in group 2 continued on the maintenance dose of recombinant human erythropoietin (18 units/kg three times a week) until the end of the trial. Patients in group 3 (n = 7) were maintained on placebo throughout the study. 4. In comparison with placebo, recombinant human erythropoietin treatment, but not desferrioxamine chelation therapy, reduced serum ferritin concentration, transferrin saturation and hepatic computed tomography density, and was associated with a rise in haemoglobin and packed cell volume. Hepatic computed tomography density, serum ferritin concentration and transferrin saturation decreased in 13 out of 14 patients (93%) during treatment with recombinant human erythropoietin. However, when the changes in hepatic computed tomography density were compared with those in the biochemical indices, we observed that the decreases in serum ferritin concentration and transferrin saturation were much slower and delayed. More specifically, within 6 months of starting recombinant human erythropoietin treatment, hepatic computed tomography density was normalized in 13 out of 14 patients (93%), whereas serum ferritin concentration and transferrin saturation were within the normal limits in only two (14%) and six patients (43%), respectively. 5. In conclusion, the strategies for monitoring the iron status of haemodialysis patients with transfusional haemosiderosis may evolve to a new level of sophistication with the introduction of computed tomography scanning. This technique has the advantage of estimating directly the effect of recombinant human erythropoietin treatment on hepatic iron storage. Hepatic computed tomography density is complementary to serum ferritin concentration and transferrin saturation in monitoring the iron status of haemodialysis patients treated with recombinant human erythropoietin.

scholarly journals Protocol and baseline data for a prospective open-label explorative randomized single-center comparative study to determine the effects of various intravenous iron preparations on markers of oxidative stress and kidney injury in chronic kidney disease (IRON-CKD)

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ahmed Ziedan ◽  
Sunil Bhandari
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Inflammatory Markers ◽  
Iron Dextran ◽  
Single Center ◽  
Open Label ◽  
Iv Iron ◽  
The Mean

Abstract Background Intravenous (IV) iron is frequently used to treat iron deficiency/anemia in patients who are unable to tolerate oral iron or the oral iron is not sufficient toreplete iron requirements. However, safety concerns regarding the potential increase in oxidative stress and other adverse effects persist and it remains unclear whether all iron preparations are equivalent. Indeed, the comparative risk of adverse events with IV iron preparations has not been extensively assessed. We hypothesize that IV iron leads to changes in oxidative stress, endothelial function, and potential renal damage depending on the iron formulation (related to the generation of “free” or catalytic labile iron) and this may result in more tubular and glomerular injury manifested as increased proteinuria and raised neutrophil gelatinase–associated lipocalin (NGAL) levels in patients with chronic kidney disease (CKD). Methods IRON-CKD is a prospective, open-label, explorative, randomized, single-center study designed to compare the safety and efficacy of three parenteral iron preparations: low-molecular-weight iron dextran–Cosmofer, iron sucrose–Venofer, and iron isomaltoside–Monofer. The study includes 40 adults who have established CKD stages 3–5 and serum ferritin (SF) of less than 200 μg/L or transferrin saturation (TS) of less than 20% (or both); they were randomly assigned in a 1:1:1:1 ratio to 200 mg iron dextran, 200 mg iron sucrose, 200 mg iron isomaltoside, or 1000 mg iron isomaltoside. After randomization, participants undergo baseline assessments and then an iron infusion. Each participant is followed up at 2 h, day 1, week 1, and months 1 and 3. At each follow-up visit, patients undergo clinical review, measurement of pulse wave velocity (PWV), blood tests for renal function, and collection of serum/plasma samples for oxidative stress and inflammatory markers. The primary outcomes are measures of oxidative stress, inflammatory markers, and markers of acute renal injury in comparison with baseline measures of each iron preparation and between each of the iron preparations. Secondary objectives include effects on hematinic profiles and hemoglobin concentrations, changes in arterial stiffness, incidence of significant side effects, and change in patients’ quality of life. Results Between October 2015 and April 2018, 521 individuals were identified as potential participants; 216 were contacted, 56 expressed an interest, 49 attended a screening visit, and 40 were confirmed to meet the eligibility criteria and were randomly assigned. The mean age was 58.3 (standard error of the mean 4.4) years, and 23 (58%) were male. All patients were white and English-speaking. The mean SF was 66.6 μg/L, TS was 21.2%, and hemoglobin was 121.6 g/L at randomization for the whole group. The mean estimated glomerular filtration rate was 27.8 mL/min, the urinary protein/creatinine ratio was 104.3 mg/mmol, and CRP was 6.65 mg/L. Discussion IRON-CKD will provide important information on the short-term effects of three preparations of IV iron in CKD patients with biochemical functional or absolute iron deficiency on measures of oxidative stress, inflammation, endothelial function, and renal injury. Trial registration European Clinical Trials Database (EudraCT) number 2010-020452-64.

scholarly journals Response predicting factors to recombinant human erythropoietin in cancer patients undergoing platinum-based chemotherapy

Cancer ◽  
2002 ◽  
Vol 95 (11) ◽  
pp. 2408-2413 ◽  
Author(s):  
Manolo González-Barón ◽  
Amdio Ordóñez ◽  
Rosa Franquesa ◽  
Manuel Constenla ◽  
Joaquin Montalar ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Recombinant Human Erythropoietin ◽  
Human Erythropoietin ◽  
Predicting Factors ◽  
Platinum Based Chemotherapy

Pharmacokinetics (PK) and Pharmacodynamics (PD) of Epoetin Alfa in Anemic Cancer Patients Receiving Cycling Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4101-4101 ◽  
Author(s):  
Wing K. Cheung ◽  
Brian Danneman ◽  
Mary Wacholtz ◽  
Henry Lau ◽  
Denis Miller
Keyword(s):  
Cancer Patients ◽  
Healthy Subjects ◽  
Fixed Dose ◽  
Epoetin Alfa ◽  
Open Label ◽  
Time Profiles ◽  
Human Erythropoietin ◽  
Safety Population ◽  
Multi Center Study ◽  
Kidney Metastasis

Abstract Epoetin alfa is a recombinant human erythropoietin (EPO). The objective of this study was to compare the PK/PD of epoetin alfa after a fixed dose (40,000 IU) once weekly (QW) regimen to those after the weight based (150 IU/kg) 3 times per week (TIW) regimen for 4 weeks in healthy subjects and for 6 weeks in anemic cancer patients. In this randomized, open-label, parallel, multi-center study, PK profiles were determined during Week 1 and Week 3 in healthy subjects. For cancer patients, PK profiles were determined during Week 1 when patients were receiving chemotherapy and an optional one during Week 3 when patients were not receiving chemotherapy. Of the 33 enrolled cancer patients who received as least one dose of Epoetin alfa (safety population), 29 were evaluable for PK and 27 were evaluable for PD. Of the safety population (82% had solid tumors), ECOG scores were 0 (48%), 1 (42%), and 2 (9%). None of the patients had bone or kidney metastasis. Their ages and body weights ranged from 31–77 yrs (mean 59.2 yrs) and 50.9 –94.1 kg (mean 70.8 kg), respectively. Mean serum EPO concentrations in the cancer patients during Week 1 were higher than during Week 3. In general, the concentration-time profiles and PK parameters of anemic cancer subjects were different from those in healthy subjects during Week 1 but similar to healthy subjects during Week 3. Mean (SD) PK parameters are listed in following table. Epoetin alfa was safe and well tolerated after the two regimens in this study. The 40,000 IU QW regimen had a higher Cmax, higher exposure to epoetin alfa/erythropoietin in serum (in terms of AUC0-7days), and a lower clearance (CL/F) than the 150 IU/kg TIW regimen. Despite these PK differences, time-profiles of changes in PD parameters and their AUC (% reticulocytes, hemoglobin, and total RBCs) were similar. Mean (SD) PK parameters 150 IU/kg TIW 150 IU/kg TIW 40,000 IU QW 40,000 IU QW 1st Week 3rd Week 1st Week 3rd Week a n=3 for Week 1 and n=2 for Week 3; b n=11 for Week 1 and n=7 for Week 3. Cancer Patients (n=14) (n=4) (n=18) (n=7) Cmax, IU/mL 414 (312) 178 (58) 1077 (510) 897 (322) AUC0-7days, mIU.h/mL 43014(37270) 21082(6909) 84205(46999) 48254(17658) CL/F, mL/h/kg 20.2(15.9) 23.6(9.5) 9.16(4.69) 13.9(7.6) T1/2, h 43.7(3.9) 41.9(14.8)a 41.9(14.8)a 38.8(11.0)b Healthy Subjects (n=6) (n=6) (n=6) (n=6) Cmax, mIU/mL 163 (54) 125 (32) 1036 (238) 909 (398) AUC0-7days, mIU.h/mL 15708(4327) 12913(3249) 47469(13301) 32969(7945) CL/F, mL/h/kg 31.2 (11.5) 36.9 (10.0) 12.6 (3.1) 17.8 (3.7) T1/2, h 25.0 (7.1) 26.0 (8.9) 28.8 (8.1) 23.7 (8.5)

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