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The addition of oral iron improves chemotherapy-induced anemia in patients receiving erythropoiesis-stimulating agents
Tan J, Du S, Zang X, Ding K, Ginzburg Y, Chen H
International journal of cancer. 2022
Abstract
Although many studies have shown that supplementation with iron and erythropoiesis-stimulating agents (ESA) is frequently used for managing chemotherapy-induced anemia (CIA), optimal combination therapy using these agents together to ameliorate anemia is not well characterized. To assess the effects of ESA combined with oral or intravenous (IV) iron on relieving CIA, PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) were searched for articles. Data collected in the articles were meta-analyzed using RevMan 5.3 software with a random-effects model. Our comprehensive search yielded 1666 potentially relevant trials. A total of 41 trials randomizing 4200 patients with CIA fulfilled inclusion criteria, including 34 Chinese articles and 7 English articles. Meta-analysis showed that treatment with both ESA and iron more effectively improved CIA relative to iron supplementation alone, with increased hemoglobin, hematocrit, red blood cell count and haematopoietic response rate. Subgroup analyses revealed iron administration, both oral and IV iron, improved anemia in ESA-treated cancer patients with CIA. Our analysis demonstrates that iron supplementation combined with ESA more effectively ameliorates CIA relative to iron supplementation alone, without regard to whether IV or oral iron was used. Together, our findings may contribute to the clinical treatment of CIA using iron therapy with or without ESA. This article is protected by copyright. All rights reserved.
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Treatment of Fanconi Anemia-Associated Head and Neck Cancer: Opportunities to Improve Outcomes
Lee RH, Kang H, Yom SS, Smogorzewska A, Johnson DE, Grandis JR
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021
Abstract
Fanconi anemia, the most frequent genetic cause of bone marrow failure, is characterized by an extreme predilection towards multiple malignancies, including a greater than 500-fold incidence of head and neck squamous cell carcinoma (HNSCC) relative to the general population. Fanconi anemia-associated HNSCC and esophageal SCC (FA-HNSCC) often present at advanced stages with poor survival. Surgical resection remains the primary treatment for FA-HNSCC, and there is often great reluctance to administer systemic agents and/or radiation therapy (RT) to these patients given their susceptibility to DNA damage. The paucity of FA-HNSCC case reports limits evidence-based management, and such cases have not been analyzed collectively in detail. We present a systematic review of FA-HNSCC treatments reported from 1966 to 2020, defining a cohort of 119 FA-HNSCC patients including 16 esophageal SCCs (131 total primary tumors), who were treated with surgery, RT, systemic therapy (including cytotoxic agents, EGFR inhibitors, or immune checkpoint inhibitors), or a combination of modalities. We summarize the clinical responses and regimen-associated toxicities by treatment modality. The collective evidence suggests that when possible, surgical resection with curative intent should remain the primary treatment modality for FA-HNSCC. Radiation can be administered with acceptable toxicity in the majority of cases, including patients who have undergone stem cell transplantation (SCT). While there is little justification for cytotoxic chemotherapy, EGFR inhibitors and tyrosine kinase inhibitors (TKIs) may be both safe and effective. Immunotherapy may also be considered. Most oncologists have little personal experience with FA-HNSCC. This review is intended as a comprehensive resource for clinicians.
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Effect of Erythropoiesis Stimulating Agents on Clinical Outcomes in Breast Cancer Patients: A Systematic Review of Randomised Controlled Trials
Sabir S, Khan YH, Khatoon M, Noreen R, Mallhi TH, Jabeen N
J Coll Physicians Surg Pak. 2020;30(3):292-298
Abstract
The impact of erythropoiesis stimulating agents (ESAs) on clinical outcomes among breast cancer patients is debatable. Current review is aimed to ascertain the efficacy of ESAs among breast cancer patients. Randomised controlled trials (RCTs) were electronically searched. Primary outcomes were mortality, blood transfusion requirements and thromboembolic events (TEEs); whereas, secondary outcomes were safety, tumor progression, anemia treatment, hemoglobin levels and quality of life (QOL). Out of 11 RCTs including 6,849 participants, 9 RCTs reported 2,312 deaths with overall mortality of 33.7%. Mortality reported for epoetin alfa (EA), epoetin beta (EB) and darbepoetin alfa (DA) was 41.24%, 73.1% and 8.99% respectively. TEEs reported for EA, EB and DA were 5.88%, 9.28% and 2.85%, respectively. Serious adverse events were 39.04%, 36.29%, 1.53% for EA, EB and DA, respectively. Tumor progression for EA and EB was 37.53% and 95.46%, respectively. No tumor progression was reported with DA. Erythropoietin reported no mortality, TEEs, serious ADRs and tumor progression. About 9% patients required transfusions during ESA therapy. Current evidence suggests that use of ESA reduces transfusion need but increases mortality and risks of TEEs.
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Impact and Outcomes of Postoperative Anaemia in Colorectal Cancer Patients: A Systematic Review
Moncur A, Chowdhary M, Chu Y, Francis N
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2020
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Editor's Choice
Abstract
OBJECTIVES Preoperative anaemia is common in colorectal cancer patients. Little attention has been given to the prevalence and consequences of postoperative anaemia. The aim of this study was to systematically review the published literature and determine the knowledge of prevalence and impact of postoperative anaemia in colorectal cancer patients. METHODS Databases, CINAHL and Medline, via EBSCO Host, were systematically searched to identify suitable articles published between 2004-2020. After an initial search, articles were screened and all eligible articles reported on prevalence of postoperative anaemia, clinical and long-term outcomes data in colorectal cancer patients undergoing surgery were included. The Risk of Bias 2.0 tool for the assessment of Randomised Controlled Trials and Risk of Bias in Non-randomised studies 1.0 tool were used for the assessment of bias in the studies selected in our review. RESULTS Six studies, one randomised control trial and five cohort studies were included with a total population size of 1714. The prevalence of anaemia at discharge of 76.6% was reported as the primary endpoint in only one study. The rate of Red Blood Cell Transfusion and length of hospital stay were found to be significantly increased in anaemic patients, while postoperative infection rate results were variable. Quality of life scores and overall survival at 5 years were significantly affected among anaemic patients as reported in two papers. CONCLUSION The available limited evidence on postoperative anaemia indicates its high prevalence with negative impact on clinical and long-term outcomes. Further research is required to standardise the measurement and address the true impact of correcting postoperative anaemia on functional and oncological outcomes.
PICO Summary
Population
Colorectal cancer patients undergoing surgery (6 studies, n= 1,714).
Intervention
Systematic review to determine the prevalence and consequences of postoperative anaemia.
Comparison
Outcome
The prevalence of anaemia at discharge of 76.6% was reported as the primary endpoint in only one study. The rate of red blood cell transfusion and length of hospital stay were found to be significantly increased in anaemic patients, while postoperative infection rate results were variable. Quality of life scores and overall survival at 5 years were significantly affected among anaemic patients as reported in two papers.
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Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update
Bohlius J, Bohlke K, Castelli R, Djulbegovic B, Lustberg MB, Martino M, Mountzios G, Peswani N, Porter L, Tanaka TN, et al
Blood advances. 2019;3(8):1197-1210
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Editor's Choice
Abstract
PURPOSE To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. RECOMMENDATIONS ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to < 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines.
PICO Summary
Population
Patients with cancer or chronic kidney disease (17 studies).
Intervention
Erythropoiesis-stimulating agents (ESAs) including biosimilars.
Comparison
Addition of iron to an ESA, placebo or best standard therapy.
Outcome
A growing body of evidence suggested that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of red blood cell transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remained limited.
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Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update
Bohlius J, Bohlke K, Lazo-Langner A
Journal of oncology practice. 2019;:Jop1900111
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Comparative effectiveness and safety of traditional Chinese medicine supporting Qi and enriching blood for cancer related anemia in patients not receiving chemoradiotherapy: a meta-analysis and systematic review
Dang Z, Liu X, Wang X, Li M, Jiang Y, Wang X, Yang Z
Drug design, development and therapy. 2019;13:221-230
Abstract
A systematic review and meta-analysis of previous randomized controlled trials of traditional Chinese medicine (TCM) supporting Qi and enriching blood in the treatment of cancer related anemia (CRA) in patients not receiving chemoradiotherapy were conducted. A total of 13 randomized controlled trials were included. Compared with the control group, better improvement was found for the level of hemoglobin (mean difference=4.57, 95% CI [1.38, 7.76], P=0.005) and overall therapeutic effect (risk ratio [RR]=1.31, 95% CI [1.18, 1.46], P<0.000) in the TCM groups. The incidence of related adverse events was not increased in the TCM groups (RR=0.54, 95% CI [0.29, 0.99], P=0.05). However, due to the relatively low quality and the small sample sizes of the included studies, the results should be interpreted with a degree of caution. Nevertheless, TCM with the role of supporting Qi and enriching blood may be a safe and effective treatment for CRA in patients not receiving chemoradiotherapy and might be considered as an alternative treatment to conventional western medicine including iron supplements and erythropoietin.
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Intravenous iron versus oral iron or observation for gastrointestinal malignancies: a systematic review
Tang GH, Dhir V, Scheer AS, Tricco AC, Sholzberg M, Brezden-Masley C
European journal of gastroenterology & hepatology. 2019
Abstract
BACKGROUND Anemia is a common condition in patients with gastrointestinal cancer. Current evidence for the use of intravenous compared with oral iron in this clinical setting is inconclusive. A systematic review was performed to assess evidence on the efficacy of intravenous iron versus oral/observation in gastrointestinal cancer patients in the preoperative and postoperative setting. MATERIALS AND METHODS We searched Medline and Embase from inception until December 2017 with no language restrictions. Outcomes included hemoglobin response, red blood cell transfusion, and adverse events. Screening, data abstraction, and risk of bias appraisal were performed by two independent reviewers. The risk of bias was assessed using the Cochrane tools for randomized and nonrandomized studies. RESULTS A total of 10 studies (three randomized-controlled trials and seven nonrandomized studies) were included. Of the six preoperative studies, five reported that hemoglobin was significantly higher in the intravenous group compared with oral iron/observation. Among the four postoperative studies, three studies suggested that hemoglobin was significantly higher in the intravenous group compared with oral iron/observation. The overall risk of bias for all randomized-controlled trials was low. Quality assessments for nonrandomized studies found the risk of bias to be moderate for four studies and critical for three studies. CONCLUSION Despite the limitations of the current body of evidence, there is a likely benefit to the use of intravenous iron in this patient population. Further confirmatory research is needed to draw empirical conclusions.
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A quick scoping review of efficacy, safety, economic, and health-related quality-of-life outcomes of short- and long-acting erythropoiesis-stimulating agents in the treatment of chemotherapy-induced anemia and chronic kidney disease anemia
Arantes LH Jr, Crawford J, Gascon P, Latymer M, Launay-Vacher V, Rolland C, Scotte F, Wish J
Critical Reviews in Oncology-Hematology.. 2018;129:79-90.
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Abstract
Erythropoiesis-stimulating agents (ESAs) are man-made forms of erythropoietin used in the treatment of anemia. This quick-scoping review of systematic literature reviews (SLRs) was conducted to define the clinical, economic, and health-related quality of life (HRQoL) outcomes for short-acting and long-acting ESAs in patients with chronic kidney disease-induced anemia (CKD-IA) and patients with chemotherapy-induced anemia (CIA). Embase, Medline, and the Cochrane Database of Systematic Reviews were searched from their establishment until October 2017. SLRs related to the use of short-acting and long-acting ESAs in the treatment of CIA and CKD-IA were included. Forty-eight studies met the inclusion criteria. The evidence suggests little difference in efficacy, HRQoL, and safety outcomes among ESA types. Cost-effectiveness and market price are likely to become determining factors driving the choice of agent. Comparative studies and costing models accounting for the utilization of biosimilars are needed to establish which ESAs are more cost-effective.Copyright © 2018. Published by Elsevier B.V.
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Erythropoietin for cancer-associated malignant anemia: A meta-analysis
Zhao F, Wang Y, Liu L, Bian M
Molecular and Clinical Oncology. 2017;6((6)):925-930.
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Abstract
The present study aimed to evaluate the effectiveness of erythropoietin (EPO) for improving cancer-associated malignant anemia. A search was performed for randomized clinical trials, conducted according to the Cochrane manual, using electronic databases including PubMed, EMBASE, the Cochrane Library and ClinicalTrails.gov up to 15 August 2015. A total of 6 eligible studies from 5 articles enrolling a total of 453 patients were entered into the current meta-analysis. Upon EPO treatment, there were significant differences in the change in hemoglobin (HB) levels compared with the placebo at short-term follow-up [mean difference (MD)=0.66; 95% confidence interval (CI), 0.14-1.18; I2=Not applicable; P=0.01) and long-term follow-up (MD=0.10; 95% CI, 0.02-0.18; I2=Not applicable; P=0.01) under the random effects model. For changes in hematocrit (HCT) compared with the placebo, the results revealed there were significant differences at short-term follow-up (MD=2.47; 95% CI, 0.75-4.19; I2=Not applicable; P=0.005) and long-term follow-up (MD=7.60; 95% CI, 6.15-9.05; I2=Not applicable; P<0.00001) under the random effects model. Compared with the placebo in short-term follow-up under the fixed effects model with homogeneity, the result was a significant difference for the transfusion ratio [relative risk (RR)=0.81; 95% CI, 0.67- 0.97; I2=34%; P=0.02) and the transfusion requirements (MD=-0.45; 95% CI, -0.92, 0.03; I2=6%; P=0.07). Funnel plots did not detect any publication bias. These results suggest that EPO was beneficial to alleviate cancer-associated anemia and improve survival outcomes for patients with cancer.
