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Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Buchrits S, Itzhaki O, Avni T, Raanani P, Gafter-Gvili A
Journal of clinical medicine. 2022;11(14)
Abstract
BACKGROUND The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. MATERIALS AND METHODS All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I(2) > 40%), in which we used a random effects model. RESULTS A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55-0.95) with a number needed to treat of 20 (95% CI 11-100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01-1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88-1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76-1.57; 8 trials). CONCLUSIONS IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.
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2.
Risk of venous thromboembolism with the erythropoiesis-stimulating agents (ESAs) for the treatment of cancer-associated anemia: a meta-analysis of randomized control trials
Zhan P, Wang Q, Qian Q, Yu LK
Chinese Clinical Oncology. 2012;1((2):):19.
Abstract
BACKGROUND In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate the overall risk of venous thromboembolism (VTE) associated with the use of ESAs, a systematic review and meta-analysis of published randomized controlled trials (RCT) was performed. METHODS The databases of PubMed and Web of Science were searched from January 1966 until December 2012 and abstracts presented at American Society of Clinical Oncology conferences held between January 2000 and December 2012 were searched to identify relevant clinical trials. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated. RESULTS Data from a total of 11,632 patients with cancer in 50 RCTs were identified and included for meta-analysis. Among those patients receiving ESAs, the summary incidences of all-grade VTE were 7.62%. Patients with cancer who received ESAs had increased VTE risks (482 events among 6,238 patients treated with ESA vs. 269 events among 5,394 control patients; RR=1.75; 95% CI, 1.49-2.05). The highest risk of VET was found in patients with ovarian and cervical cancer for 2.45 (1.12-5.33). CONCLUSIONS The use of ESAs was significantly associated with an increased risk of developing VTE in cancer patients receiving this drug. The risks of VTE may vary with various tumor types.
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3.
The use of erythropoiesis-stimulating agents in patients with non-myeloid hematological malignancies: a systematic review
Shehata N, Walker I, Meyer R, Haynes AE, Imrie K, The Cancer Care Ontario Hematology Disease Site Group
Annals of Hematology. 2008;87((12):):961-73.
Abstract
The effectiveness of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with non-myeloid hematological malignancies needs to be assessed as the response to their administration is not uniform and their cost is high. We conducted a systematic review (SR) of the literature to identify reports of the effect of ESAs on survival, quality of life (QOL), transfusion requirements, and anemia. The entries to MEDLINE, EMBASE, and the Cochrane Library databases, and abstracts published in the proceedings of the annual meetings of the American Society of Clinical Oncology and the American Society of Hematology were searched. Seventeen reports and five abstracts of randomized trials fulfilled prospective criteria for inclusion. Five trials reported on survival; three failed to detect differences between groups and two demonstrated inferior survival in patients allocated to an ESA. Seven trials and three abstracts reported on QOL with four articles and three abstracts describing improvements in patients allocated to erythropoietin. However, important methodologic limitations were identified in these reports. Seven randomized controlled trials reported a reduction in the proportion of patients transfused. The absolute risk reduction in transfusions ranged from 15% to 24%. This is the only SR that assesses the use of erythropoiesis-stimulating agents specifically in patients with hematological malignancies. We conclude that available data evaluating ESAs in patients with hematologic malignancies demonstrate that these agents reduce transfusion requirements. Limitations of these data preclude conclusions that these agents improve QOL. More data are required to confirm the inferior survival associated with ESAs.
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4.
Effectiveness of erythropoietin in the treatment of patients with malignancies: methods and preliminary results of a Cochrane review
Bohlius JF, Langensiepen S, Engert A, Schwarzer G, Bennett CL
Best Practice & Research. Clinical Haematology. 2005;18((3):):449-54.
Abstract
Cancer and cancer therapy-associated anemia may have an impact on tumor response and overall survival. Additionally, anemia represents an important economic factor. Therefore, therapeutic alternatives such as erythropoietin (EPO) and red blood cell transfusions have to be evaluated systematically. The effectiveness of recombinant human EPO to prevent or alleviate anemia in patients with malignant disease was determined. Randomized controlled trials comparing prophylaxis or treatment of anemia with EPO plus red blood cell transfusion (RBCT) or RBCT only in patients with malignant disease undergoing antineoplastic therapy were included. The endpoints needed for RBCT were hematological response (hemoglobin increase of 2g/dL or hematocrit increase of 6%), tumor response, and overall survival. Medical databases (Cochrane Library, MEDLINE, EMBASE) and conference proceedings were searched (1985-2001). Full-text and abstract publications were included as well as unpublished data. Data extraction and quality assessment were done in duplicate. All authors were contacted to obtain missing data. Out of 33 eligible studies, 27 trials with 3,287 randomized patients were included.
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5.
Systematic review and meta-analysis of randomized controlled trials of erythropoietin in multiple myeloma
Soares HP, Kumar A, Silvestris F, Djulbegovic B
Blood. 2004;104((11):):70a.. Abstract No. 232.
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6.
Epoietin in the treatment of malignant disease: a comprehensive meta-analysis
Bohlius JF, Langensiepen S, Schwarzer G, Engert A
Blood. 2002;100((11):): Abstract No. 3430.
