ferric-carboxymaltose and Colorectal-Neoplasms

A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia.. In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment.. Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202).. Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation.. Vifor Pharma.

Topics: Adult; Anemia, Iron-Deficiency; Colorectal Neoplasms; Dietary Supplements; Female; Hemoglobins; Humans; Iron; Male

Recent clinical guidelines suggest that treatment of postoperative anaemia in colorectal cancer surgery with intravenous iron reduces transfusion requirements and improves outcomes. The study aimed at comparing two intravenous iron regimens in anaemic patients after colorectal cancer surgery.. This was a single-centre, open-label, randomised, controlled trial in patients undergoing elective colorectal cancer surgery. Patients with moderate to severe anaemia (haemoglobin [Hb] <11 g/dL) after surgery were randomly assigned 1:1 to receive ferric carboxymaltose (FC; 1,000 mg, single dose) or iron sucrose (IS; 200 mg every 48 hours until covering the total iron deficit or discharge). Randomisation was stratified by Hb level: <10 g/dL (Group A) or ≥10-10.9 (Group B). The primary endpoint was the change in Hb concentration at postoperative day 30. Secondary endpoints included iron status parameters, transfusion requirements, complications, and length of hospital stay.. From September 2015 to May 2018, 104 patients were randomised (FC 50, IS 54). The median intravenous iron dose was 1,000 mg and 600 mg in the FC and IS groups, respectively. There were no between-group differences in mean change in Hb from postoperative day 1 to postoperative day 30 (FC: 2.5 g/dL, 95% CI: 2.1-2.9; IS: 2.4 g/dL, 95% CI: 2.0-2.8; p=0.52), in transfusion requirements or length of stay. The infection rate was lower in the FC group compared with the IS group (9.8% vs 37.2%, respectively).. The administration of approximately 500 mg of IS resulted in an increase in Hb at postoperative day 30 similar to that of 1,000 mg of FC, but it was associated with a higher infection rate. Future research will be needed to confirm the results, and to choose the best regime in terms of effectiveness and side effects to treat postoperative anaemia in colorectal cancer patients.

Topics: Administration, Intravenous; Anemia; Anemia, Iron-Deficiency; Colorectal Neoplasms; Ferric Compounds; Ferric Oxide, Saccharated; Hemoglobins; Humans; Iron; Maltose

Patients with colorectal cancer (CRC) often present with associated anaemia which is usually present at the time of diagnosis and is aggravated during the postoperative period due to blood loss during the surgery process. Several guidelines advocate for the treatment of postoperative anaemia in these patients in order to prevent complications and allogeneic blood transfusions. However, there are no publications to shed light on the effectiveness of intravenous iron (IVI) administration after CRC surgery and the optimal dose and regimen. We have started a clinical trial with the objective of comparing the effectiveness of 1000 mg of ferric carboxymaltose with fractionated iron sucrose 200 g/48 h for the treatment of postoperative anaemia, by measuring the change of haemoglobin (Hb) levels from postoperative day (POD) 1 to POD 30.. We designed an open label randomised controlled trial to compare two postoperative IVI treatment regimens. Patients aged > 18 years undergoing CRC surgery, with Hb < 11 g/dL on POD 1 are randomly assigned to receive either 1000 mg of ferric carboxymaltose (single dose) or 200 g/48 h of iron sucrose. The main study endpoint will be the change from POD 1 to POD 30 in Hb levels and the key secondary endpoint the percentage of patients with Hb levels ≥ 13 g/dL at POD 30. Other secondary endpoints include: changes in iron metabolism parameters (Fe, ferritin, transferrin, % saturated trasferrin) at POD 30; total doses of iron received; number of postoperative transfusions; compliance with oral iron treatment; number of medical and surgical complications; adverse reactions reported by the patient; use of health resources after surgery; and changes in quality of life (QoL). It has been estimated that a sample of 48 patients per group will allow detecting a difference of 0.75 g/dL in Hb in the change in Hb levels from POD 1 to POD 30.. The results of this study will confirm if the single dose of 1000 mg ferric carboxymaltose should be preferred in front of the fractionated doses and in which type of patients this regimen should be used preferably.. European Union Clinical Trials Register, EudraCT 2015-001005-13 . Registered on 6 January 2015.

Topics: Anemia; Colorectal Neoplasms; Ferric Compounds; Ferric Oxide, Saccharated; Humans; Infusions, Intravenous; Maltose; Postoperative Complications; Randomized Controlled Trials as Topic

Treatment of preoperative anaemia is recommended as part of patient blood management, aiming to minimize perioperative allogeneic red blood cell transfusion. No clear evidence exists outlining which treatment modality should be used in patients with colorectal cancer. The study aimed to compare the efficacy of preoperative intravenous and oral iron in reducing blood transfusion use in anaemic patients undergoing elective colorectal cancer surgery.. Anaemic patients with non-metastatic colorectal adenocarcinoma were recruited at least 2 weeks before surgery and randomized to receive oral (ferrous sulphate) or intravenous (ferric carboxymaltose) iron. Perioperative changes in haemoglobin, ferritin, transferrin saturation and blood transfusion use were recorded until postoperative outpatient review.. Some 116 patients were included in the study. There was no difference in blood transfusion use from recruitment to trial completion in terms of either volume of blood administered (P = 0·841) or number of patients transfused (P = 0·470). Despite this, increases in haemoglobin after treatment were higher with intravenous iron (median 1·55 (i.q.r. 0·93-2·58) versus 0·50 (-0·13 to 1·33) g/dl; P < 0·001), which was associated with fewer anaemic patients at the time of surgery (75 versus 90 per cent; P = 0·048). Haemoglobin levels were thus higher at surgery after treatment with intravenous than with oral iron (mean 11·9 (95 per cent c.i. 11·5 to 12·3) versus 11·0 (10·6 to 11·4) g/dl respectively; P = 0·002), as were ferritin (P < 0·001) and transferrin saturation (P < 0·001) levels.. Intravenous iron did not reduce the blood transfusion requirement but was more effective than oral iron at treating preoperative anaemia and iron deficiency in patients undergoing colorectal cancer surgery.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Colorectal Neoplasms; Elective Surgical Procedures; Erythrocyte Transfusion; Female; Ferric Compounds; Ferrous Compounds; Follow-Up Studies; Hematinics; Humans; Injections, Intravenous; Male; Maltose; Middle Aged; Postoperative Complications; Preoperative Care; Prospective Studies; Treatment Outcome

At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer.. In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland.. This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity.. ClincalTrials.gov: NCT02243735 .

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Clinical Protocols; Colorectal Neoplasms; Dietary Supplements; Female; Ferric Compounds; Ferrous Compounds; Fumarates; Hematinics; Humans; Infusions, Intravenous; Male; Maltose; Middle Aged; Preoperative Care; Treatment Outcome; Young Adult

The study aimed to analyse the feasibility and efficacy of administration of a single intravenous iron infusion (IVI) in the preoperative optimization of colorectal cancer patients with anaemia.. Twenty patients were recruited at least 14 days before the planned date of surgery. A single 1000 mg dose of ferric carboxymaltose (Ferinject) was administered as an outpatient procedure. Blood samples were taken at recruitment prior to drug administration (REC), on the day of surgery prior to any intervention (DOS) and on the first postoperative day. Allogeneic red blood cell transfusions (ARBT) and outcomes were recorded from recruitment throughout the study period.. There was a significant median rise in haemoglobin levels (Hb) from REC to DOS of 1.8 g/dl [interquartile range (IQR) 0.75-2.45, P < 0.001] for the entire cohort. Two patients received ARBT preoperatively, and for those not transfused preoperatively (n = 18), this incremental Hb rise remained significant (P < 0.001, median 1.65 g/dl, IQR 0.5-2.3). Of these patients, those who responded to IVI had higher erythropoietin (EPO) levels at recruitment (P < 0.01) and lower recruitment Hb values, transferrin-saturation (TSAT) and C-reactive protein (CRP) levels (P < 0.05). REC Hb (Rs = -0.62, P < 0.01), REC TSAT levels (Rs = -0.67, P < 0.01) and REC EPO (Rs = 0.69, P < 0.01) correlated with the magnitude of treatment change in Hb levels. Five patients received ARBT until the fourth postoperative day, which was significantly fewer than predicted (P < 0.05).. IVI can be administered preoperatively in the outpatient clinic to colorectal cancer patients with anaemia, with associated reduction in ARBT use and increase in Hb levels.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; C-Reactive Protein; Colorectal Neoplasms; Erythrocyte Transfusion; Erythropoietin; Feasibility Studies; Female; Ferric Compounds; Hemoglobins; Humans; Infusions, Intravenous; Length of Stay; Male; Maltose; Middle Aged; Pilot Projects; Postoperative Complications; Preoperative Care; Transferrins

Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.

Topics: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cell Proliferation; Colorectal Neoplasms; Female; Ferric Compounds; Ferrous Compounds; Humans; Iron; Male; Maltose; Middle Aged