Benefits and risks of using erythropoiesis-stimulating agents (ESAs) in lung cancer patients: Study-level and patient-level meta-analyses

Vansteenkiste, Johan; Glaspy, John A.; Henry, David H.; Ludwig, Heinz; Pirker, Robert; Tomita, Dianne; Collins, Helen; Crawford, Jeffrey

doi:10.1016/j.lungcan.2011.12.015

Cited by 45 publications

(36 citation statements)

References 39 publications

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“…During the follow-up period, a significantly higher incidence of death from lung ADC was found in patients with low pretreatment EPOR levels as compared with those of high EPOR levels. Although large-scale meta-analyses of clinical trials on erythropoiesis-stimulating agents in various tumor types [28], including NSCLC [29], suggest no effect of these drugs on patients' prognosis, our results, therefore, support an effect of rHuEPOα either directly or indirectly reducing pulmonary ADC progression. The current preliminary study, however, has to be confirmed in further studies in additional cohorts of patients with lung ADC.…”

Section: Discussioncontrasting

confidence: 47%

Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma

et al. 2013

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Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III–IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2’-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

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Section: Discussioncontrasting

confidence: 47%

Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma

et al. 2013

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“…For example, in a pooled analysis of randomized, double-blind, placebo-controlled trials in patients with chemotherapy-induced anemia receiving DA or placebo (n=2122), DA had no impact on mortality, progression-free survival or disease progression [14]. Similarly, three metaanalyses -one of studies in patients with lymphoproliferative malignancies [15], one in patients with lung cancer [16] and one broader analysis of oncology studies [17] -found no effect of ESAs on survival or disease progression.…”

Section: Discussionmentioning

confidence: 99%

Darbepoetin alfa administration in patients with non-Hodgkin lymphoma and chemotherapy-induced anemia receiving (±R)CHOP

et al. 2013

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IMPACT NHL was a multicenter, observational study in adults with non-Hodgkin lymphoma receiving CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with or without rituximab. Erythropoietin-stimulating agent treatment was given according to routine clinical practice and physician preference. In a subanalysis, outcomes were evaluated in 207 patients who received darbepoetin alfa (DA). The most common reason (81%) for initiating DA was low/declining hemoglobin (Hb) concentration. Mean (±standard deviation) duration of DA exposure was 8.8 ± 6.9 weeks (mean number of doses, 5.1 ± 4.6). Overall, 23% of patients had chemotherapy and DA treatment synchronized more than 75% of the time. At the time of DA initiation, 67% of patients had Hb concentrations in the guideline-recommended range (9-11 g/dl). Of 89 patients with Hb concentrations <10 g/dl at DA initiation and still receiving DA 5 weeks later, 92% (Kaplan-Meier) achieved Hb concentrations 10-12 g/dl between week 5 and at the end of treatment.

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“…The latter effectively eliminated the use of ESAs in patients being treated for cure. Although significant controversy exists regarding the impact of ESA use on survival in cancer patients with CAA, the impact of FDA and CMS policy on ESA use is clear [13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Impact of a Patient Blood Management Program and an Outpatient Anemia Management Protocol on Red Cell Transfusions in Oncology Inpatients and Outpatients

et al. 2016

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Background. Patient blood management (PBM) programs are associated with reduced transfusion usage, reduced hospital costs, and improved patient outcomes. The application of PBM principles in patients with malignant disease might achieve similar results. However, this population presents unique challenges. The aim of the present study was to investigate the impact of a PBM program on blood usage and patient outcomes in cancer patients, particularly in the setting of restricted use of erythropoiesis-stimulating agents (ESAs). Materials and Methods. A retrospective observational study was performed of patients admitted with a primary diagnosis of malignancy treated at Eastern Maine Medical Center as inpatients or outpatients, or both, from January 2008 through July 2013. Results. The proportion of inpatients and outpatients receiving ESAs decreased from 2.9% in 2008 to 1.1% in 2013 (p < .001). During the same period, an increase occurred in the mean dose of intravenous (IV) iron from 447 mg (95% confidence interval [CI], 337–556) to 588 mg (95% CI, 458–718). The mean red blood cell (RBC) units transfused per inpatient and outpatient episode decreased from 0.067 to 0.038 unit (p < .001). In inpatients, significant increases occurred in the proportion of single-unit RBC transfusions (p < .001) and patients infused with IV iron (p = .02), and significant decreases in the mean pretransfusion hemoglobin (p = .02) and RBC transfusion rate (p = .04). In-hospital mortality and length of stay did not change significantly during this period. Conclusion. Despite the decreased use of ESA therapy, the implementation of a PBM program and outpatient anemia management protocol in cancer patients at our medical center was associated with significant reductions in RBC usage.

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Benefits and risks of using erythropoiesis-stimulating agents (ESAs) in lung cancer patients: Study-level and patient-level meta-analyses

Cited by 45 publications

References 39 publications

Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma

Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma

Darbepoetin alfa administration in patients with non-Hodgkin lymphoma and chemotherapy-induced anemia receiving (±R)CHOP

Impact of a Patient Blood Management Program and an Outpatient Anemia Management Protocol on Red Cell Transfusions in Oncology Inpatients and Outpatients

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