Iron Deficiency In Cancer Patients Research Articles

Anemia and iron deficiency in cancer patients: the role of intravenous iron supplements (a literature review)

Anemia in patients with malignancies is a common disorder that has a markedly negative impact on quality of life and overall prognosis. The pathogenesis of anemia is complex and multifactorial, depending on the type and stage of malignancy, nutritional status, renal function, age and gender, cytostatic drug, dose, and chemotherapeutic regimen, with iron deficiency often being the main and potentially treatable factor for anemia. In cancer patients, it can be caused by various concomitant mechanisms, including bleeding (e.g., in malignant gastrointestinal tumors or after surgery), malnutrition, medication, and hepcidin-induced iron sequestration in macrophages, with subsequent iron-deficient erythropoiesis. The variety of clinical manifestations of anemia makes it challenging to establish universal criteria to develop optimal treatments. Current therapy for anemia in malignant tumors includes replacement therapy with an iron supplement, erythropoiesis-stimulating agents (erythropoietins), and blood transfusions. However, blood transfusions should be minimized due to the high risks and costs. Therapy with an iron supplement is an effective approach to correcting the iron deficiency. It can increase the efficacy of erythropoiesis-stimulating drugs and reduce the need for blood transfusions. Published guidelines suggest the wide use of intravenous iron supplements. This article discusses possible approaches to treating iron deficiency in cancer patients in various clinical settings. We build on current guidelines and emphasize the need for further research in this area.

69P Transferrin saturation shows high prevalence of iron deficiency in cancer patients under adjuvant and neo-adjuvant treatment

While iron deficiency (ID) in cancer patients is frequent, it is likely under-diagnosed and under-treated, in particular in patients without anaemia or at an early stage of the disease. Also, ID diagnosis is rarely based on the transferrin coefficient saturation (TSAT) which is very sensitive in patients with inflammatory diseases. We previously showed that ID was frequent in patients under metastatic treatment. Here, we aimed to assess the prevalence of ID based on TSAT index in cancer patients treated at an early stage of the disease.

Prevalence of iron deficiency in cancer patients: The French prospective CARENFER study.

e15617 Background: Despite the potential deleterious consequences of iron deficiency (ID) in patients with cancer, under-diagnosis is frequent and existence of ID based on both serum ferritin concentration and transferrin coefficient saturation (TSAT) index is rarely determined. The CARENFER Study aimed to assess prospectively the prevalence of ID, anemia and iron deficiency anemia (IDA) in cancer patients. Methods: The study was conducted in France from May to July 2019, as a prospective cross-sectional survey carried out in 15 oncology units. The analysis focused on 1221 patients with different types of solid malignant tumors. Serum ferritin and iron concentrations, TSAT index and hemoglobin (Hb) level were determined. Based on ESMO 2018 Guidelines, ID was defined as ferritin < 100 μg/L or TSAT < 20%, and then categorized as either absolute ID (ferritin < 100 μg/L) or functional ID (ferritin ≥ 100μg/L and TSAT < 20%). Anemia was defined as Hb level ≤ 11 g/dL. Iron deficiency anemia (IDA) was defined according to ESMO 2018 Guidelines. The prevalence of ID, anemia and IDA was estimated using Agresti-Coull 95% confidence interval. Results: Patient’s median age was 63 years (55% women and 45% men). 89.4% of patients were currently under treatment for their cancer, mainly by chemotherapy (75.4%). The proportion of cancer patients with ferritin level < 100 μg/L was 20.5% [18.3-22.9] and 50.6% [47.8-53.4] of patients had a TSAT index < 20%. Overall, ID was found in 57.9% [55.1-60.6] of patients, with absolute ID accounting for 36% of all ID cases. 36.0% of patients were anemic and among them, IDA was reported in 21.8% [19.6-24.2] of patients. The type of cancer treatment did not influence the ID status as ID was also present in 57.4% of untreated cancer patient. Conclusions: This study highlights the high prevalence of ID in cancer patients, whether or not concomitantly associated with anemia or treatment. These results emphasize the need to better management of ID in cancer thereby optimizing overall patient care. Clinical trial information: NCT03924271.

Association of serum iron and response to immune checkpoint inhibitors (ICIs) in metastatic clear cell renal cell carcinoma (mccRCC).

723 Background: ICIs have improved survival in mRCC patients (pts), yet response rates (RR) to these treatments are variable. Biomarkers predictive of response to ICIs may improve outcomes for mccRCC pts. Genes that promote tumor-specific iron accumulation such as hepcidin (HAMP) or transferrin (TF) are significantly correlated with decreased overall survival in clear cell RCC (TCGA-KIRC). Iron deficiency in cancer patients is positively correlated with tumor stage and inversely proportional to treatment response (PMID: 23567147). Here, we investigate whether serum iron profile may be associated with response to ICIs in mccRCC pts. Methods: Clinical data was obtained from an mRCC registry at the Huntsman Cancer Institute, University of Utah. Analyses were limited to mccRCC pts who had serum iron studies within 6 months before initiating an ICI and had been assessed for RR. ICIs included nivolumab + ipilimumab, atezolizumab, or nivolumab alone. Responses were defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by RECIST criteria. Clinical benefit (CB) was defined as CR + PR + SD. Descriptive statistics were used to assess associations between iron stores and response to ICIs and IMDC criteria. Results: 36 pts met all aforementioned eligibility criteria (29 were of IMDC intermediate risk, 7 were of IMDC poor risk). 5 pts received a first-line ICI, and the remaining 31 pts received ICIs as salvage therapy. Pts with CB had a significantly higher median serum iron level compared to those with no CB (59 vs 38.5 ug/dL; p=0.024). Furthermore, pts with normal transferrin saturation (TSAT %) were more likely to derive CB from ICIs (p=0.048). No association was found between serum ferritin (a marker of inflammation and tissue iron) and response to ICIs. Conclusions: In this hypothesis-generating study, increased serum iron, and TSAT levels within the normal range are associated with an increased likelihood of response to ICIs in pts with mccRCC. Once validated, these results may establish serum iron profile as a predictive marker of response to ICIs, in addition to providing the rationale for ruling out iron deficiency before starting ICIs.

Effectiveness and safety of ferric carboxymaltose to treat iron deficiency anemia in cancer patients.

e23153 Background: Most cancer patients are faced with anemia during the disease course. Iron deficiency (ID) is one of the major causes of anemia in cancer patients.Bleeding, malabsorption and organ dysfunction may cause iron deficiency in cancer patients. Anemia may result in a decrease in the patient's performance and delayed chemotherapy. Administration of intravenous (IV) iron is a therapeutic option in cancer patients with iron-deficiency related anemia. In this study we analyzed effectiveness and tolerability of ferric carboxymaltose in cancer patients with iron deficiency anemia Methods: This is a retrospective analysis of 603 cancer patients who were treated with ferric carboxymaltose for anemia and iron-deficiency between October 2014 and April 2017 in a tertiary cancer clinic. Demographic data, cancer diagnoses, pre- and post-treatment hemoglobin levels, pre-treatment ferritin, serum iron, and transferrin saturation (TSA) levels were recorded. Results: The median age of the population was 55 (22-90) years, and 52% were male. Of 603 patients, 47.9% (n = 289) had gastrointestinal malignancies and 17% (n = 103) had breast cancer. A total of 331 patients (55%) received cytotoxic chemotherapy and 272 patients (45%) were not on anti-cancer treatment. Median dose of the ferric carboxymaltose is 1000 mg (500-2000). The median baseline hemoglobin, ferritin and TSA were 10.7 (7-13) g/dl, 28 (2.9-2200) ng/ml and 9.3 (1-19) %, respectively. The median hemoglobin level at the 12th week of treatment was 12.7 g/dl. The median increase in hemoglobin was 2.9 (-0.10-6.9) g/dl in patients whom received cytotoxic chemotherapy. Only 2 patients had allergic reaction during IV ferric carboxymaltose administration and treatment was discontinued. Conclusions: Intravenous-iron improved hemoglobin levels both in actively treated and not-actively treated cancer patients. The effect has been shown in the first 3 months after injection. This approach is safe and tolerable. However, the impact of tumor progression on IV iron replacement is unclear, further studies are required.

Iron deficiency and cancer – clinical implications

Anemia is a frequent complication in oncologic patients, being encountered both at the moment of cancer diagnosis and during different oncologic therapies. The presence of anemia, regardless of the cause or mechanism, in oncologic patients adversely affects the quality of life, the outcome of the neoplastic disease and the adherence to treatment. The mechanisms involved in the appearance of anemia in oncologic patients are intricated. Iron deficiency is a frequent cause of anemia in oncologic patients. This de­fi­cien­cy is noticed in approximately 50% of patients with solid and hematological tumors. In oncologic patients, the pre­va­lent mechanism for iron deficiency is the functional mechanism. In this case, the iron stores are reduced due to the underlying oncologic condition or due to inflammatory processes associated to cancer treatments. Iron deficiency in cancer patients is often underestimated, mainly due to the difficulty of defining iron deficiency on the basis of usual laboratory markers. The current therapeutic options of cancer anemia include blood transfusions, iron substitution and erythropoietin-stimulating agents.

Anemia and Iron Deficiency in Cancer Patients: Role of Iron Replacement Therapy.

Anemia in cancer patients is quite common, with remarkable negative impacts on quality of life and overall prognosis. The pathogenesis is complex and typically multifactorial, with iron deficiency (ID) often being a major and potentially treatable contributor. In turn, ID in cancer patients can be due to multiple concurring mechanisms, including bleeding (e.g., in gastrointestinal cancers or after surgery), malnutrition, medications, and hepcidin-driven iron sequestration into macrophages with subsequent iron-restricted erythropoiesis. Indeed, either absolute or functional iron deficiency (AID or FID) can occur. While for absolute ID there is a general consensus regarding the laboratory definition (that is ferritin levels <100 ng/mL ± transferrin saturation (TSAT) <20%), a shared definition of functional ID is still lacking. Current therapeutic options in cancer anemia include iron replacement, erythropoietic stimulating agents (ESAs), and blood transfusions. The latter should be kept to a minimum, because of concerns regarding risks, costs, and limited resources. Iron therapy has proved to be a valid approach to enhance efficacy of ESAs and to reduce transfusion need. Available guidelines focus mainly on patients with chemotherapy-associated anemia, and generally suggest intravenous (IV) iron when AID or FID is present. However, in the case of FID, the upper limit of ferritin in association with TSAT <20% at which iron should be prescribed is a matter of controversy, ranging up to 800 ng/mL. An increasingly recognized indication to IV iron in cancer patients is represented by preoperative anemia in elective oncologic surgery. In this setting, the primary goal of treatment is to decrease the need of blood transfusions in the perioperative period, rather than improving anemia-related symptoms as in chemotherapy-associated anemia. Protocols are mainly based on experiences of Patient Blood Management (PBM) in non-oncologic surgery, but no specific guidelines are available for oncologic surgery. Here we discuss some possible approaches to the management of ID in cancer patients in different clinical settings, based on current guidelines and recommendations, emphasizing the need for further research in the field.

Iron deficiency in cancer patients.

Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients.

Iron metabolism and iron supplementation in cancer patients.

SummaryIron deficiency and iron deficiency-associated anemia are common complications in cancer patients. Most iron deficient cancer patients present with functional iron deficiency (FID), a status with adequate storage iron, but insufficient iron supply for erythroblasts and other iron dependent tissues. FID is the consequence of the cancer-associated cytokine release, while in absolute iron deficiency iron stores are depleted resulting in similar but often more severe symptoms of insufficient iron supply. Here we present a short review on the epidemiology, pathophysiology, diagnosis, clinical symptoms, and treatment of iron deficiency in cancer patients. Special emphasis is given to intravenous iron supplementation and on the benefits and limitations of different formulations. Based on these considerations and recommendations from current international guidelines we developed recommendations for clinical practice and classified the level of evidence and grade of recommendation according to the principles of evidence-based medicine.

Current Practice In Diagnosis and Treatment of Chemotherapy-Induced Anemia In Five European Countries – A Patient Record Study

AbstractAbstract 1512 Introduction:The most comprehensive study on the prevalence and treatment of anemia in cancer patients in Europe (ECAS) dates from 2004. A reevaluation of treatment patterns for anemia in cancer patients (ACT, 2009) focused on patients treated with erythropoiesis-stimulating agents (ESAs). The study reported here aimed to assess current practice in the diagnosis and treatment of chemotherapy-induced anemia (CIA) as well as the role of iron therapy. Methods:Onco-hematologists in 5 European countries (France, Germany, UK, Spain, Switzerland; Jun - Oct 2009) completed forms asking for patient demographics, TNM stage of cancer, status of anemia, tests for diagnosis or confirmation of anemia, treatment, and if applicable details of iron therapy (used product, dosing regimen, reasons for prescription). Records of the last 5 CIA patients treated for anemia within the last 6 months were analyzed. Results are presented as mean [range] across countries. Results:244 physicians (194 hospital-, 50 office-based) reported 1209 cases. Lymphoma (23%), myeloma (13%), lung (14%) and breast (12%) cancer were the most frequent cancer types. Metastatic disease was present in 66% of 662 patients with solid tumors. Tests to confirm anemia comprised mainly hemoglobin (Hb; 89% [85-95%]) and serum ferritin (48% [32-56%]). Transferrin saturation (TSAT) was only tested in 13% [9-23%] of patients. In 11% of patients, Hb was the only test performed. At diagnosis, 71% [62-82%] presented with Hb ≤ 10 g/dL, the EMA/FDA recommended cut-off level for ESA treatment initiation. Ferritin ≤ 30 ng/mL, commonly used as an indicator of absolute iron deficiency, was seen in 17% [8-21%] of patients. However, 29% [18-80%] of patients tested for TSAT had levels ≤ 20%, indicating insufficient available iron for effective erythropoiesis. Anemia treatment included an ESA in 48% [13-81%] of patients. Although only 15% [9-22%] of patients had a Hb ≤ 8 g/dL at diagnosis, 54% [27-80%] received at least one blood transfusion in the 6 months prior to the survey. Iron treatment (oral or i.v.) was given in 23% [8-56%] of patients of whom, 62% received iron in combination with an ESA, 31% received iron in combination with red blood cell transfusion and 23% received iron alone; 35% in these three groups received i.v. iron. ‘Quick onset of action’ was stated as main reason for the use of i.v. iron in 35% of cases. Interestingly, the decision for oral iron treatment was justified by ‘Effective when used in combination’ in 31% of cases although clinical trials have shown that oral iron in contrast to i.v. iron does not add to the benefit of ESA therapy. Discussion:Despite pivotal trials showing the efficacy of i.v. iron supplementation in ESA-treated cancer patients and the potential to reduce required ESA doses or blood transfusions, the majority of anemic cancer patients are still treated with ESAs or blood transfusions alone. Only 23% receive iron therapy in routine practice. Compared to the patients who received anemia treatment in the 2004 ECAS study, this study reveals only moderately higher rates of iron treated patients (23 vs. 17%) whereas the frequency of blood transfusions is substantially higher (54 vs. 38%). Furthermore, only one third of iron treated patients receive i.v. iron despite of international guidelines recommending i.v. iron for the treatment of absolute and functional iron deficiency in cancer patients and oral iron has not been proven effective in these patients. This gap in the awareness about iron metabolism in specific patient populations is also reflected in the underuse of TSAT determination, a reliable and widely available marker of absolute and functional iron deficiency. Diagnosis of iron deficiency is still mainly based on ferritin although NCCN guidelines consider patients with ferritin levels up to 800 ng/mL as functionally iron deficient if TSAT is <20%. This study confirms the need to increase awareness about the impact of cancer on iron metabolism and about evidence-based recommendations for i.v. iron supplementation. Disclosures:Beguin:Vifor Pharma: Honoraria, Membership on an Advisory Board. Aapro:Vifor Pharma: Honoraria, Membership on an Advisory Board. Bokemeyer:Vifor Pharma: Membership on an Advisory Board. Glaspy:Vifor Pharma: Membership on an Advisory Board. Hedenus:Vifor Pharma: Honoraria, Membership on an Advisory Board. Littlewood:Vifor Pharma: Honoraria, Membership on an Advisory Board. Ludwig:Vifor Pharma: Honoraria, Membership on an Advisory Board. Österborg:Vifor Pharma: Honoraria, Membership on an Advisory Board. Mitchell:Vifor Pharma: Employment.

Investigation of the relationship between serum hepcidin and prohepcidin in anemia of cancer (AoC) patients with the anemia of inflammation (AI)

20644 Background: The anemia observed in cancer patients is complex and may result from a combination of causes; iron deficiency, inflammation (AI), toxicity related to therapy, marrow infiltration, dyserythropoiesis and others. Determining effective anemia treatment can therefore be complex, requiring a combination of diagnostic tests. Algorithms exist to quantify the contribution of iron deficiency versus AI but are complex and as yet unvalidated. Hepcidin, a peptide reducing iron availability for erythropoiesis is induced by inflammation, and elevated hepcidin levels may underlie functional iron deficiency in cancer patients. Hepcidin levels have been suggested as an appropriate marker of AI but in the absence of a readily available serum hepcidin assay, a commercial assay to detect prohepcidin (DRG ELISA) has been used. Several studies have attempted to establish a relationship between prohepcidin and inflammation. Here we have contrasted the quantification of prohepcidin with mature hepcidin to defin...