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

Intravenous iron has become the standard of care in patients with renal failure receiving treatment with erythropoiesis stimulating agents (ESAs) to treat true and functional iron deficiency and to prevent its development in haemodialysis patients. In cancer-related anaemia, several recently published, randomised studies suggested that intravenous iron improved haemoglobin response rates in ESA-treated patients compared to those treated with oral iron or placebo. The data supporting the efficacy of intravenous iron instead of oral iron in this setting are increasingly persuasive but larger randomised trials are needed before definitive recommendations are made.     

A prospective randomized,controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy

Abstract. Khalafallah A, Dennis A, Bates J, Bates G, Robertson IK, Smith L, Ball MJ, Seaton D, Brain T, Rasko JEJ Launceston General Hospital (LGH), Australia; University of Tasmania, Australia; and Centenary Institute, University of Sydney, NSW, Australia) A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern Med 2010; 268 : 286–295. Background. Iron deficiency anaemia is the most common deficiency disorder in the world, affecting more than one billion people, with pregnant women at particular risk. Objectives and design. We conducted a single site, prospective, nonblinded randomized‐controlled trial to compare the efficacy, safety, tolerability and compliance of standard oral daily iron versus intravenous iron Subjects. We prospectively screened 2654 pregnant women between March 2007 and January 2009 with a full blood count and iron studies, of which 461 (18%) had moderate IDA. Two hundred women matched for haemoglobin concentration and serum ferritin level were recruited. Interventions. Patients were randomized to daily oral ferrous sulphate 250 mg (elemental iron 80 mg) with or without a single intravenous iron polymaltose infusion. Results. Prior to delivery, the intravenous plus oral iron arm was superior to the oral iron only arm as measured by the increase in haemoglobin level (mean of 19.5 g/L vs. 12 g/L; P < 0.001); the increase in mean serum ferritin level (222 μg/L vs. 18 ug/L; P < 0.001); and the percentage of mothers with ferritin levels below 30 μg/L (4.5% vs. 79%; P < 0.001). A single dose of intravenous iron polymaltose was well tolerated without significant side effects. Conclusions. Our data indicate that intravenous iron polymaltose is safe and leads to improved efficacy and iron stores compared to oral iron alone in pregnancy‐related IDA.     

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

Background

Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED.

Materials and methods

From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes.

Results

Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed.

Discussion

Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.     

Neoadjuvant intra-arterial versus intravenous chemotherapy in colorectal cancer

To investigate the clinical benefits of transcatheter arterial infusion chemotherapy compared with intravenous chemotherapy in patients with colorectal cancer (CRC).From May 2013 to March 2018, 83 patients (50 men and 33 women) with surgically proven CRC were retrospectively included. Before surgery, 62 patients received conventional systemic chemotherapy, and 21 transcatheter arterial chemotherapy. Basic characteristics, disease control rate (DC), adverse reactions, postoperative complications, and toxicity profiles were collected and compared between the 2 groups.The sigmoid colon (43.37%) was the most common primary tumor location, and the least was the transverse colon (6.02%). Most lesions invaded the subserosa or other structures T3-4 (78.31%), and other lesions invaded the muscular layer T1-2 (21. 69%). The overall DC was 80.65% in the intravenous chemotherapy group and 90.48% in the arterial chemotherapy group (P < .05). Adverse events included myelosuppression and gastrointestinal reactions such as nausea, vomiting, diarrhea, abnormal liver function, and neurotoxicity, which were significantly less common in the intra-arterial group than in the intravenous group (P < .05). Postoperative complications included abdominal infection (11.29% vs 14.29%), intestinal obstruction (6.45% vs 4.76%), anastomotic bleeding (1.61% vs 0.00%), and anastomotic fistula (6.45% vs 4.76%) in the intravenous and intra-arterial groups, respectively (P > .05).Preoperative transcatheter arterial infusion chemotherapy is a safe and effective neoadjuvant chemotherapy measure for CRC with fewer adverse reactions and a higher overall DC.     

Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for iron deficiency anemia in obstetric and gynecologic patients: A systematic review and meta-analysis

Introduction:Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients.Methods:We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3.Results:We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], −0.07 to 015; I² = 0%; P = 0.48) and ferritin levels (MD, −0.42 ng/mL; 95% CI, −1.61 to 0.78; I² = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25–1.08; I² = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06–36.76; I² = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35–0.80; I² = 0%; P = 0.003). Serious adverse events were not reported in any group.Conclusion:FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity.Trial registration:The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905).     

Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double‐blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate‐to‐severe HSRs, including anaphylaxis, or moderate‐to‐severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate‐to‐severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least‐squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.     

Use of erythropoiesis stimulating agents and intravenous iron for cancer and treatment-related anaemia: the need for predictors and indicators of effectiveness has not abated

Cancer and treatment-related anaemia is a significant clinical problem. Erythropoiesis stimulating agents (ESA) improve anaemia and ultimately enhance patients' quality of life. However, about one-third of patients do not respond to ESA administration, mostly because of the impaired supply of iron to the erythroid marrow (functional iron deficiency). Concomitant administration of intravenous (IV) iron may improve responsiveness. The use of baseline predictors of response to ESA and of indicators of appropriateness of response and iron availability should allow targeted therapeutic interventions with both ESA and IV iron. Several biochemical and haematological indicators of response and of iron balance have been studied, but firm criteria for their use have not yet been rigorously established. The commonly used early predictive markers of response to ESA, such as baseline endogenous erythropoietin levels and an increase in haemoglobin, reticulocytes, and soluble transferrin receptor levels during ESA treatment, have not proved reliable due to their low sensitivity and specificity. Traditional markers of iron availability, such as serum ferritin and transferrin saturation display interpretation pitfalls. The need for predictors and indicators of responsiveness to ESA and IV iron is still current and clinically relevant.     

A comparison between intravenous iron polymaltose complex (Ferrum Hausmann®) and oral ferrous fumarate in the treatment of iron deficiency anaemia in pregnancy

Abstract: Anaemia is the most common medical disorder in pregnancy with iron deficiency anaemia accounting for the majority of cases. Over 90% of the iron deficiency anaemia is due to red cell iron deficiency associated with depleted iron stores and deficient intake. The two main modalities of treating iron deficiency anaemia are oral or parenteral iron. Ferrous Hausmann® (iron dextrin) is the latest iron preparation which can be used for intravenous parenteral administration as a total dose infusion. This study compares the efficacy of Ferrum Hausmann® with oral ferrous fumarate therapy in the treatment of iron deficiency anaemia in pregnancy. Our study shows that treatment with intravenous Ferrum Hausmann® (iron dextrin) resulted in a significantly better level and rate of increase of haemoglobin (p<0.001). Serum ferritin, which is the best indicator of iron stores, was significantly higher (p<0.001) in the intravenous group. Other indices of iron status such as serum iron, serum transferrin and zinc protoporphyrin also showed a significant improvement in the intravenous group compared to those given oral iron. The results suggest that intravenous iron as a total dose infusion is able to replenish iron stores more efficiently, completely and at a faster rate than oral iron therapy, thus providing the fuel for stimulation of full erythopoiesis compared to oral iron. There were also no reports of any adverse reactions with intravenous iron dextrin, whereas there were a considerable proportion of women on oral iron therapy who reported side effects. In conclusion, intravenous iron therapy with Ferrous Hausmann® (iron dextrin) is a suitable, effective and safe alternative to oral iron therapy in the treatment of iron deficiency anaemia in pregnancy.     

Clinical significance of serum iron and ferritin in patients with colorectal cancer

To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 ± 38.6g/dl vs 93.0 ± 32.1 g/dl and 107.1 ± 32.9g/dl, respectively (p < 0.001).=" the=" mean=" value=" of=" serum=" ferritin=" levels=" in=" patients=" with=" early=" and=" advanced=" colorectal=" cancer=" was=" also=" significantly=" decreased=" compared=" with=" controls,=" 80.5=" ±=" 35.0ng/ml=" (p=">< 0.01)=" and=" 48.8=" ±=" 72.8=" ng/ml=" (p=">< 0.001),=" respectively,=" vs=" 117.1=" ±=" 46.8=" ng/ml.=" however,=" there=" was=" no=" significant=" difference=" between=" mean=" serum=" iron=" levels=" in=" patients=" with=" early=" colorectal=" cancer=" and=" controls.=" eighteen=" (78.3%)=" of=" the=" 23=" patients=" with=" advanced=" colorectal=" cancer=" and=" 3=" (16.7%)=" of=" the=" 18=" patients=" with=" early=" colorectal=" cancer=" had=" serum=" iron=" levels=" below=">g/dl and serum ferritin levels below 60ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer.     

A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial

BACKGROUND AIMS:  Anemia is a common complication of inflammatory bowel diseases (IBD) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation, ferric carboxymaltose (FeCarb), in comparison with oral ferrous sulfate (FeSulf) in reducing iron deficiency anemia (IDA) in IBD.
METHODS:  Two hundred patients were randomized in a 2:1 ratio (137 FeCarb:63 FeSulf) to receive FeCarb (maximum 1,000 mg iron per infusion) at 1-wk intervals until the patients' calculated total iron deficit was reached or FeSulf (100 mg b.i.d.) for 12 wk. The primary end point was change in hemoglobin (Hb) from baseline to week 12.
RESULTS:  The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority ( P = 0.6967). Response (defined as Hb increase of >2.0 g/dL) was higher for FeCarb at week 2 ( P = 0.0051) and week 4 ( P = 0.0346). Median ferritin increased from 5.0 to 323.5 μg/L at week 2, followed by a continuous decrease in the FeCarb group (43.5 μg/L at week 12). In the FeSulf group, a moderate increase from 6.5 to 28.5 μg/L at week 12 was observed. Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively.
CONCLUSIONS:  FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores.     

The impact of timing of intravenous iron supplementation on preoperative haemoglobin in patients scheduled for major surgery

BackgroundAnaemia is frequent and an independent risk factor for morbidity and mortality in patients undergoing surgery. Iron deficiency (ID) is the main cause for anaemia and can be corrected by intravenous (IV) iron. The aim of this study was to investigate the timing of preoperative IV iron supplementation on preoperative haemoglobin (Hb) level.Materials and methodsSurgical patients were screened for the presence of anaemia and ID from November 2015 to January 2020. In case of ID or iron deficiency anaemia (IDA), patients received IV iron supplementation. The timing of IV iron supplementation on preoperative Hb level was analysed by days and time frames clustered by 5 days before surgery.ResultsIn total, 404 patients with IV iron supplementation were analysed. In all patients, IV iron was administered with a median (interquartile range [IQR]) of 3.0 (1.0; 9.0) days before surgery. Preoperative Hb level increased steadily starting from 6 days (0.13 [±1.2] g/dL) until 16 days before surgery (1.75 [±1.1] g/dL). Group comparison revealed a median preoperative Hb change of −0.2 (−0.5; 0.2) g/dL for days 1–5, 0.2 (0.0; 0.7) g/dL for days 6–10, 0.7 (0.2; 1.1) g/dL for days 11–15, 0.7 (0.2; 1.8) g/dL for days 16–20, 0.9 (0.3; 1.7) g/dL for days 21–25, 1.5 (0.4; 2.6) g/dL for days 26–30, and 0.6 (0.0; 1.7) g/dL for >31 days. Three patients received multiple administrations of IV iron which resulted in an increase in Hb of >4 g/dL.DiscussionSupplementation of IV iron to increase Hb concentration preoperatively may be most effective if administered at least ten days before surgery.     

Safety and efficacy of intravenous iron isomaltoside for correction of anaemia in patients with inflammatory bowel disease in everyday clinical practice

Aims: Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD), who are often treated with intravenous iron. This observational study aimed to investigate the effectiveness and safety of iron isomaltoside in routine practical care of IDA in IBD patients.

Methods: The study included 197 IBD patients designated for treatment with iron isomaltoside. Treatment was administered according to routine practice. Data were recorded at baseline and after approximately 4, 8, and 16 weeks. Efficacy data included haemoglobin (Hb) levels and haematinics, while safety data included adverse drug reactions and safety laboratory variables.

Results: Patients received a mean (range) cumulative dose of 1304 (100–3500) mg iron isomaltoside. Hb increased from 10.7(±1.6) g/dL at baseline to 13.1(±1.5) g/dL at the final visit. In addition, serum iron, ferritin and transferrin saturation increased and soluble transferrin receptor decreased. Calprotectin decreased, as did IBD symptom scores, Harvey–Bradshaw Index (Crohn’s disease) and partial Mayo score (Ulcerative colitis). About 8% of patients reported transient adverse reactions, most commonly skin reactions, nausea and vomiting, and 2% SAEs, most frequently tachycardia.

Conclusion: Iron isomaltoside was demonstrated to be effective and had a good safety profile in IBD patients in everyday clinical practice in Germany.     

Pre-transfusion management of children with severe malarial anaemia: a randomised controlled trial of intravascular volume expansion

Symptomatic severe malarial anaemia (SMA) has a high fatality rate of 30-40%; most deaths occur in children awaiting blood transfusion. Blood transfusion services in most of Africa are not capable of delivering adequate supplies of safe blood in a timely manner to critically ill children with SMA. Contrary to widely held belief, hypovolaemia, rather than heart failure, has emerged as a common complication in such children. We examined the safety of pre-transfusion management (PTM) by volume expansion, aimed at stabilizing children and obviating the urgency for blood transfusion. Kenyan children with severe falciparum anaemia (haemoglobin <5 g/dl) and respiratory distress were randomly assigned to 20 ml/kg of 4.5% albumin or 0.9% saline or maintenance only (control) while awaiting blood transfusion. PTM was apparently safe since it did not lead to the development of pulmonary oedema or other adverse events. There was no significant difference in the primary outcome [mean percentage reduction in base excess between admission and 8 h (95% confidence interval)] between the control group 42% (19-66%) albumin group 44% (32-57%) and saline group 36% (16-57%); adjusted analysis of variance F=0.31, P=0.7. However, the number of children requiring emergency interventions was significantly greater in the control group, four of 18 (22%) than the saline group 0 of 20 (P=0.03). We have established the safety of this PTM in children with SMA whilst awaiting blood transfusion at a hospital with an adequate blood-banking program. The impact on mortality should be assessed where blood transfusion services are unable to supply emergency transfusions.