-
1.
Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial
Talboom K, Borstlap WAA, Roodbeen SX, Bruns ERJ, Buskens CJ, Hompes R, Tytgat Kmaj, Tuynman JB, Consten ECJ, Heuff G, et al
The Lancet. Haematology. 2023
-
-
-
Full text
-
Editor's Choice
Abstract
BACKGROUND 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. METHODS 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. FINDINGS 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). INTERPRETATION 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. FUNDING Vifor Pharma.
PICO Summary
Population
Patients with colorectal cancer and iron deficiency anaemia scheduled for elective curative resection; enrolled in the FIT trial in the Netherlands and Italy (n= 202).
Intervention
Intravenous ferric carboxymaltose (n= 96).
Comparison
Oral ferrous fumarate (n= 106).
Outcome
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]), 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]).
-
2.
Oxidized Regenerated Cellulose Versus Calcium Alginate in Controlling Bleeding From Malignant Wounds: A Randomized Controlled Trial
Firmino F, Villela-Castro D, Santos Vlcg
Cancer nursing. 2023
Abstract
BACKGROUND There is no consensus on the best intervention for topical management of bleeding in malignant wounds. Although surgical hemostatic dressings are recommended, the use of calcium alginate (CA) is frequent among practitioners. OBJECTIVE The aim of this study was to evaluate the hemostatic efficacy of oxidized regenerated cellulose (ORC) and CA dressing in the management of bleeding from malignant wounds resulting from breast cancer. METHODS This was a randomized open clinical trial. The outcomes measured were total time to hemostasis and the number of hemostatic products used. RESULTS Sixty-one patients were potentially eligible for the study, 1 did not consent, and 32 were assessed to be ineligible, resulting in a sample of 28 who were randomized to 2 study groups. Total time to hemostasis was 93.8 seconds in the ORC group, with an average of 30.1 seconds (95% confidence interval, 18.6-189 seconds), and 67 seconds in the CA group, with an average of 30.4 seconds (confidence interval, 21.7 seconds to imprecise upper limit). The main difference was 26.8 seconds. Kaplan-Meier log-rank test, and Cox model showed no statistical significance (P = 0.894). A total of 18 hemostatic products were used in the CA group and 34 in the ORC group. No adverse effects were identified. CONCLUSIONS Although no significant differences were identified in terms of time, more hemostatic products were used in the ORC group, highlighting the effectiveness of CA. IMPLICATIONS FOR PRACTICE Calcium alginate may be the first choice in the management of bleeding in malignant wounds, favoring nursing in the most immediate hemostatic actions.
-
3.
Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial
Yang, T. C., Chen, W. C., Hou, M. C., Chen, P. H., Lee, P. C., Chang, C. Y., Lu, H. S., Chen, Y. J., Hsu, S. J., Huang, H. C., et al
Gut. 2023
Abstract
OBJECTIVE This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER NCT01970748.
-
4.
The ICaRAS randomised controlled trial: Intravenous iron to treat anaemia in people with advanced cancer - feasibility of recruitment, intervention and delivery
Dickson EA, Ng O, Keeler BD, Wilcock A, Brookes MJ, Acheson AG
Palliative medicine. 2023;:2692163221145604
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
BACKGROUND Anaemia is highly prevalent in people with advanced, palliative cancer yet sufficiently effective and safe treatments are lacking. Oral iron is poorly tolerated, and blood transfusion offers only transient benefits. Intravenous iron has shown promise as an effective treatment for anaemia but its use for people with advanced, palliative cancer lacks evidence. AIMS To assess feasibility of the trial design according to screening, recruitment, and attrition rates. To evaluate the efficacy of intravenous iron to treat anaemia in people with solid tumours, receiving palliative care. DESIGN A multicentre, randomised, double blind, placebo-controlled trial of intravenous iron (ferric derisomaltose, Monofer(®)). Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires (EQ5D5L, QLQC30, and the FACIT-F) over 8 weeks. (ISRCTN; 13370767). SETTING/PARTICIPANTS People with anaemia and advanced solid tumours who were fatigued with a performance status ⩽2 receiving support from a specialist palliative care service. RESULTS 34 participants were randomised over 16 months (17 iron, 17 placebo). Among those eligible 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Results indicated that intravenous iron may be efficacious at improving participant haemoglobin, iron stores and select fatigue specific quality of life measures compared to placebo. CONCLUSION The trial was feasible according to recruitment and attrition rates. Intravenous iron increased haemoglobin and may improve fatigue specific quality of life measures compared to placebo. A definitive trial is required for confirmation.
PICO Summary
Population
People with anaemia and advanced solid tumours, enrolled in the Intravenous Iron for Cancer Related Anaemia Symptoms (ICaRAS) trial (n= 34).
Intervention
Intravenous iron (n= 17).
Comparison
Placebo: sodium chloride (n= 17).
Outcome
Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires over 8 weeks. Among those eligible, 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Compared to baseline, there was a significant rise in haemoglobin, ferritin, and transferrin saturation % at weeks 4 and 8 for participants in the iron group but not the placebo group. Anaemia resolution was achieved in 39% of intravenous iron participants by week 8 compared to 8% of the placebo group.
-
5.
Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial
Al-Samkari H, Kolb-Sielecki J, Safina SZ, Xue X, Jamieson BD
The Lancet. Haematology. 2022;9(3):e179-e189
Abstract
BACKGROUND Chemotherapy-induced thrombocytopenia is common and causes chemotherapy dose reductions or treatment delays, bleeding, and suboptimal oncological outcomes. We aimed to evaluate avatrombopag, a thrombopoietin receptor agonist that increases platelet counts, in patients with non-haematological cancer and platelet counts lower than 50 ×10(9) cells per L. METHODS In this randomised, double-blind, placebo-controlled, phase 3 study, patients aged 18 years or older at 71 hospitals or cancer treatment centres in China, Hungary, Poland, Russia, Serbia, Ukraine, and the USA and with ovarian, bladder, or lung cancer receiving chemotherapy who had severe thrombocytopenia were randomly assigned (2:1) to oral avatrombopag 60 mg or oral placebo once daily given 5 days before and after chemotherapy, with randomisation stratified by number of chemotherapy drugs used. Patients, investigators, and data collectors were masked to group allocation. Eligibility required two previous lines of chemotherapy or fewer, an ECOG performance status of 2 or less, and no previous history of chemotherapy-induced thrombocytopenia. The composite primary endpoint was the proportion of responders not requiring platelet transfusion or either a 15% or more chemotherapy dose reduction or a 4-day or more chemotherapy delay due to thrombocytopenia following study treatment until the start of the subsequent cycle. Analyses were done on the intention-to-treat and per protocol populations. Safety was analysed in all patients who received at least one dose of avatrombopag. The trial is registered with ClinicalTrials.gov, NCT03471078, and has been completed. FINDINGS Between Oct 12, 2018, and June 28, 2020, 122 patients were enrolled and randomly assigned to receive avatrombopag (n=82) or placebo (n=40). Median follow-up was 31 days (IQR 22-61). Similar proportions of patients reached the primary endpoint in the avatrombopag and placebo groups (intention-to-treat: 57 [70%, 95% CI 58-79] of 82 vs 29 [73%, 95% CI 56-85] of 40; difference -3·0% (95% CI -21·6 to 15·6); p=0·72; per protocol: 51 [85%, 95% CI 73-93] of 60 vs 27 [84%, 95% CI 67-95] of 32; 0·6% (95% CI -20·8 to 22·1); p=0·96). 15 (18%) of 82 patients had serious adverse events in the avatrombopag group and eight (20%) of 40 in the placebo group, of which thrombocytopenia was most common (4 [5%] of 82 and 4 [10%] of 40 patients). Common grade 3-4 treatment-emergent adverse events were neutropenia (22 [27%] of 82 and 16 [40%] of 40 patients), leukopenia (19 [23%] of 82 and 5 [13%] of 40), anaemia (16 [20%] of 82 and 9 [23%] of 40), and thrombocytopenia (16 [20%] of 82 and 14 [35%] of 40). Most adverse events were considered unrelated to study drug. No treatment-related deaths were reported. INTERPRETATION In this population of patients with non-haematological malignancies who are relatively chemotherapy naive, chemotherapy-induced thrombocytopenia treatment outcomes were similar between the avatrombopag and placebo groups. Given its safety and ability to augment platelet counts in patients with chemotherapy-induced thrombocytopenia, evaluation of avatrombopag in populations with more persistent chemotherapy-induced thrombocytopenia is warranted. FUNDING Dova Pharmaceuticals, a Sobi company.
-
6.
Romiplostim for chemotherapy-induced thrombocytopenia: Efficacy and safety of extended use
Wilkins CR, Ortiz J, Gilbert LJ, Yin S, Mones JV, Parameswaran R, Mantha S, Soff GA
Research and practice in thrombosis and haemostasis. 2022;6(3):e12701
Abstract
BACKGROUND Chemotherapy-induced thrombocytopenia (CIT) is common during treatment with antineoplastic therapies and may adversely impact chemotherapy dose intensity. There is no approved therapy for CIT. In our recent phase II randomized study, romiplostim led to correction of platelet counts in 85% of treated patients and allowed resumption of chemotherapy, with low rates of recurrent CIT in the first two cycles or 8 weeks of chemotherapy. However, there is a lack of long-term data on the efficacy and safety of romiplostim in CIT. OBJECTIVES To analyze efficacy and safety of romiplostim in the patients in the phase 2 study, who received romiplostim for ≥1 year. PATIENTS/METHODS Twenty-one patients remained on romiplostim for ≥1 year. We analyzed the effect of romiplostim on platelet counts, absolute neutrophil counts, and hemoglobin, as well as impact on ongoing chemotherapy. We also tracked venous or arterial thrombotic events. RESULTS During the study period, romiplostim was effective in preventing reduction of chemotherapy dose intensity due to CIT. Fourteen of the 20 (70%) analyzable patients experienced no episode of CIT, 4 subjects experienced a single chemotherapy dose delay due CIT, and 2 patients required a chemotherapy dose reduction. Platelet counts were preserved throughout the duration of the extension analysis. One patient experienced a proximal deep vein thrombosis, and one patient experienced multiple tumor-related ischemic events. CONCLUSIONS Long-term use of romiplostim for treatment of CIT was effective and safe, with no evidence of resistance or increased risk of thrombosis.
-
7.
Perioperative changes in haemoglobin and ferritin concentrations from preoperative intravenous iron isomaltoside for iron deficiency anaemia in patients with colorectal cancer: A pilot randomised controlled trial
Fung PLP, Lau VNM, Ng FF, Leung WW, Mak TWC, Lee A
PloS one. 2022;17(6):e0270640
Abstract
BACKGROUND Patients with colorectal cancer have a high risk of iron deficiency anaemia (IDA) due to chronic tumour induced blood loss, a reduced dietary iron intake from poor nutrition or gastrointestinal malabsorption. This pilot, double blinded, randomised controlled trial (RCT) examined the effect and feasibility of using preoperative iron isomaltoside for treating iron deficiency anaemia. METHODS Forty eligible adults with IDA were randomised to receive either intravenous iron isomaltoside (20 mg.kg-1 up to 1000 mg over 30 minutes) or usual preoperative care (control) three weeks before scheduled colorectal surgery. The primary outcomes were perioperative changes in haemoglobin and ferritin concentrations. RESULTS The recruitment rate was 78% of all eligible referred patients (1.9 patients/month). The haemoglobin and ferritin concentrations were higher in the iron isomaltoside group than the control group over the perioperative period (group*time interaction P = 0.042 and P < 0.001 respectively). Mean haemoglobin change from baseline to before surgery was higher in the iron isomaltoside group (7.8, 95% CI: 3.2 to 12.3 g.l-1) than the control group (1.7, 95% CI: -1.9 to 5.3 g.l-1) [mean difference 6.1, 95% CI: 0.3 to 11.8 g.l-1; P = 0.040]. The ferritin change from baseline to before surgery between groups was large in favour of the iron isomaltoside group (mean difference 296.9, 95% CI: 200.6 to 393.2 μg.l-1; P < 0.001]. There were no differences between groups in packed red blood cell transfusions needed, surgical complications, quality of recovery and days (alive and) at home within 30 days after surgery. CONCLUSION Iron isomaltoside therapy was safe and had a minimal effect on perioperative changes in haemoglobin concentration. Given the slow recruitment and new evidence emerging during the conduct of this study, conducting a multi-centre RCT based on the current pilot trial protocol is unlikely to be feasible. TRIAL REGISTRATION ClinicalTrials.gov NCT03565354.
-
8.
Randomized trial of sucrosomial iron supplementation in patients with chemotherapy-related anemia treated with ESA
Zuccarini A, Cicognini D, Tancredi R, Ferrari A, Rizzo G, Lasagna A, Caccialanza R, Cavanna L, Orlandi E, Biasini C, et al
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2022
Abstract
BACKGROUND Iron supplementation improves the erythropoiesis-stimulating agents' (ESAs) response in chemotherapy-related anemia. The primary aim of our study is to assess the efficacy of sucrosomial iron, a new oral iron formulation, in cancer patients with chemotherapy-induced anemia treated with ESAs. The secondary objectives included the efficacy into two subgroups of patients (iron replete and functional iron deficiency) between the two study arms, safety and the effect on transfusion need. METHODS In this randomized, multicentre, open-label, phase III clinical trial, 60 cancer patients were enrolled. Each patient was randomly assigned (1:1) to receive 12 weeks of oral sucrosomial iron at the dose of 30 mg daily in combination with ESAs or no supplementation to ESA treatment. The endpoint considered for efficacy was the proportion of patients achieving complete hematological response at 12 weeks (increase in Hb > 2 g/dL from baseline, without RBC transfusions in the previous 28 days or achieving Hb ≥ 12 g/dL). RESULTS There was a statistically significant association between oral sucrosomial iron supplementation in combination with ESAs and the achievement of a complete hematological response. This response was achieved within 12 weeks by 31% of patients in the control group and by 52% of patients supplemented with oral sucrosomial iron. A trend of greater response in sucrosomial iron arm was found in both subgroups. No difference was observed about safety and transfusion need. CONCLUSIONS Sucrosomial iron is well tolerated and its combination with ESAs improves the hematological response in cancer patients with chemotherapy-related anemia. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION This study has been reviewed by the Institutional Ethics Committee of the IRCCS Policlinico San Matteo Foundation, Pavia, Italy (28/04/2015; prot. N. 20,150,002,059), and by the Institutional Ethics Committee of the other Italian oncological centers involved in this study.
-
9.
Efficacy and Safety of Ferric Carboxymaltose Infusion in Reducing Anemia in Patients Receiving Chemotherapy for Nonmyeloid Malignancies: a Randomized, Placebo-Controlled Study (IRON CLAD)
Makharadze T, Boccia R, Krupa A, Blackman N, Henry DH, Gilreath JA
American journal of hematology. 2021
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
PURPOSE Erythropoiesis-stimulating agents (ESA) are effective for chemotherapy-induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. METHODS This Phase 3, 18-week, double-blind, placebo-controlled study randomized adults with ≥4 weeks of chemotherapy remaining for treatment of nonmyeloid malignancies with CIA to FCM (two 15 mg/kg infusions 7 days apart; maximum dose, 750 mg single/1500 mg total) or placebo. The primary efficacy endpoint was percentage of patients with decreases in hemoglobin (Hb) ≥0.5 g/dL from weeks 3 to 18; the key secondary efficacy endpoint was change in Hb from baseline to week 18. Inclusion criteria included: (Hb) 8-11 g/dL, ferritin 100-800 ng/mL, and transferrin saturation (TSAT) ≤35%. RESULTS In 244 patients (n=122, both groups), the percent who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs 35.3%; P=0.01). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs 0.87 g/dL) but significantly greater with FCM with baseline Hb ≤9.9 g/dL (1.08 vs 0.42 g/dL; P=0.01). The percent with ≥1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs 54%; P=0.01), occurring in a median 43 versus 85 days (P=0.001). Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). CONCLUSION FCM monotherapy effectively maintained Hb and was well tolerated in CIA. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Patients receiving chemotherapy for non-myeloid malignancies with chemotherapy-induced anaemia (CIA), enrolled in the IRON-CLAD study conducted at 58 sites in the United States, Bulgaria, Georgia, Hungary, and Poland (n= 244).
Intervention
Ferric carboxymaltose (FCM) infusions (n= 122).
Comparison
Placebo (n= 122).
Outcome
The percentage of patients who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs. 35.3%). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs. 0.87 g/dL) but significantly greater with FCM with baseline Hb <= 9.9 g/dL (1.08 vs. 0.42 g/dL). The percent with >= 1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs. 54%), occurring in a median 43 versus 85 days. Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). FCM monotherapy effectively maintained Hb and was well tolerated in CIA.
-
10.
Intravenous iron is non-inferior to oral iron regarding cell growth and iron metabolism in colorectal cancer associated with iron-deficiency anaemia
Al-Hassi HO, Ng O, Evstatiev R, Mangalika M, Worton N, Jambrich M, Khare V, Phipps O, Keeler B, Gasche C, et al
Scientific reports. 2021;11(1):13699
Abstract
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.