The role of iron in the management of chemotherapy-induced anemia in cancer patients receiving erythropoiesis-stimulating agents

Mhaskar, Rahul; Wao, Hesborn; Miladinović, Branko; Kumar, Amit; Djulbegoviĉ, Benjamin

doi:10.1002/14651858.cd009624.pub2

Cited by 46 publications

(36 citation statements)

References 69 publications

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“…The primary literature review included 15 meta-analyses of RCTs 1,2,13-25 and two RCTs. 6,26 Three meta-analyses 15,20,22 addressed the addition of iron to an ESA. The remaining 12 meta-analyses 1,2,13,14,[16][17][18][19]21,[23][24][25] addressed ESA versus control (placebo or best standard therapy).…”

Section: Resultsmentioning

confidence: 99%

“…The use of supplemental iron with an ESA was evaluated in three metaanalyses. 15,20,22 Compared with an ESA alone, a 2016 Cochrane review by Mhaskar et al 20 reported that the combination of an ESA and iron increased the likelihood of hematopoietic response (RR, 1.17; 95% CI, 1.09 to 1.26) and reduced the likelihood of RBC transfusion (RR, 0.74; 95% CI, 0.60 to 0.92) without significantly affecting risk of thromboembolism (RR, 0.95; 95% CI, 0.54 to 1.65) or quality of life (standardized mean difference, 0.01; 95% CI, 20.10 to 0.12). Intravenous (IV) iron provided a greater benefit than oral iron with respect to mean change in HgB level (IV iron mean difference, 0.84; 95% CI, 0.21 to 1.46; P = .009; oral iron mean difference, 0.07; 95% CI, 20.19 to 0.34; P = .59; P = .03 for interaction).…”

Section: Recommendation 10mentioning

confidence: 99%

“…However, the results were not consistent across all other hematologic outcomes, and the quality of adverse outcomes reporting was poor. 15,20,22 Safety has been better studied in a systematic review and meta-analysis in patients with CKD, which showed no difference in mortality or serious adverse events in patients receiving intravenous iron, although there were more episodes of hypotension with IV iron. 44…”

Section: Recommendation 10mentioning

confidence: 99%

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Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

Bohlius

Bohlke

Castelli

et al. 2019

JCO

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107

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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 .

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Section: Resultsmentioning

confidence: 99%

Section: Recommendation 10mentioning

confidence: 99%

Section: Recommendation 10mentioning

confidence: 99%

See 1 more Smart Citation

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

Bohlius

Bohlke

Castelli

et al. 2019

JCO

Self Cite

107

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show abstract

“…Moreover, inhibition of eryptosis may counteract anemia, a common clinical disorder of malignancy and its treatment [111][112][113][114][115][116][117][118][119]. Anemia in malignancy is at least in part due to eryptosis, which is triggered by both, the disease and by cytostatic treatment [13, 15, 44, 47, 50, 53-55, 62, 65, 74, 76, 88, 111, 120-128].…”

Section: Discussionmentioning

confidence: 99%

“…Anemia in malignancy is at least in part due to eryptosis, which is triggered by both, the disease and by cytostatic treatment [13, 15, 44, 47, 50, 53-55, 62, 65, 74, 76, 88, 111, 120-128]. Anemia correlates with unfavourable outcome [112,113,[129][130][131][132] and drugs are thus needed which counteract tumor growth and by the same token inhibit eryptosis. Despite its inhibitory effect on eryptosis, sonidegib causes,…”

Section: Discussionmentioning

confidence: 99%

Sonidegib, a Novel Inhibitor of Suicidal Erythrocyte Death

Bhuyan¹,

Sahu²,

Cao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The Hedgehog pathway disrupting drug sonidegib is used in the treatment of basal cell carcinoma. Side effects of sonidegib include anemia, which could result either from impaired erythropoiesis or from loss of erythrocytes e.g. due to suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage. Eryptosis is stimulated by cell stress, including energy depletion, hyperosmotic shock, oxidative stress and excessive increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i). The present study explored, whether sonidegib exerts an effect on eryptosis. Methods: Human erythrocytes have been treated with energy depletion (glucose withdrawal for 48 hours), hyperosmotic shock (addition of 550 mM sucrose for 6 hours), oxidative stress (addition of 0.3 mM tert-butylhydroperoxide [tBOOH] for 50 min) or Ca²⁺ ionophore ionomycin (1 µM for 60 min) in absence and presence of sonidegib (2-6 µg/ ml). After treatment flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, and cell volume from forward scatter. Hemolysis was estimated from the hemoglobin concentration in the supernatant. Results: In the absence of cell stress exposure to sonidegib did not significantly modify annexin-V-binding or forward scatter, but triggered hemolysis. Energy depletion, hyperosmotic shock, oxidative stress and ionomycin, all markedly and significantly increased the percentage of annexin-V-binding erythrocytes, and decreased the forward scatter. Sonidegib significantly blunted the effect of energy depletion, hyperosmotic shock, and oxidative stress, but not of ionomycin on annexin-V-binding. Sonidegib further significantly blunted the effect of energy depletion, but not of hyperosmotic shock, oxidative stress, and ionomycin on forward scatter. Conclusions: Sonidegib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion, hyperosmotic shock and oxidative stress.

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Iron Supplementation for Chemotherapy-Induced Anemia in Patients Receiving Erythropoiesis-Stimulating Agents

Mhaskar

Djulbegoviĉ

2016

JAMA Oncol

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The role of iron in the management of chemotherapy-induced anemia in cancer patients receiving erythropoiesis-stimulating agents

Cited by 46 publications

References 69 publications

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

Sonidegib, a Novel Inhibitor of Suicidal Erythrocyte Death

Iron Supplementation for Chemotherapy-Induced Anemia in Patients Receiving Erythropoiesis-Stimulating Agents

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