Bohlius, J., Tonia, T., Nuesch, E., Juni, P., Fey, M.F., Egger, M., & Bernhard, J. (2014). Effects of erythropoiesis-stimulating agents on fatigue- and anaemia-related symptoms in cancer patients: Systematic review and meta-analyses of published and unpublished data. British Journal of Cancer, 111, 33–45. 

STUDY PURPOSE: To critically evaluate and quantify the effects of erythropoiesis-stimulating agents (ESAs) on quality of life (QoL) in patients with cancer; to examine the effects of ESAs on patient-rated fatigue and anamia-related symptoms; and to identify groups of patients who may benefit most from treatment with ESAs

 

TYPE OF STUDY: Systematic review and meta-analysis

DATABASES USED: Updated literature searches from previous meta-analyses on ESAs (Bohlius et al., 2006a, 2006b, 2009a, 2009b) in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and databases of conference proceedings for the years 2008 to January 2011; screened reference lists of relevant meta-analyses and clinical trials registries (US Clinical Trials Registry; International Standard Randomised Controlled Trial Number); information from study protocols and reports obtained from ESA manufacturers (Amgen, Thousand Oaks, CA, USA; Johnson & Johnson, New Brunswick, NJ, USA; Hoffmann-La Roche, Basel, Switzerland) and clinical study groups for a previous IPD meta-analysis (Bohlius et al, 2009a, b); QoL results in clinical trials registries (http://clinicaltrials.gov/; http://www.isrctn.org/).

 

KEYWORDS: Epoetin or darbepoetin and QoL, fatigue, anemia-related symptoms (not explicitly stated)

 

INCLUSION CRITERIA: Randomized controlled trials (RCTs) that compared epoetin or darbepoetin with a placebo or best standard of care, which assessed fatigue and anaemia-related symptoms in patients with cancer receiving or not receiving anticancer treatment; studies that prospectively evaluated QoL using a validated or generally accepted instrument with a planned sample size of > 50 participants per study arm or 100 participants in total; trials using different types of iron supplementation were included and evaluated in stratified analysis.

 

EXCLUSION CRITERIA: Trials with high-dose myeloablative chemotherapy regimens followed by stem cell transplantation, trials in patients with myelodysplastic syndromes and acute leukemia, and trials using ESAs for short-term preoperative treatment

TOTAL REFERENCES RETRIEVED = 304 (2,018 documents initially identified; 1,714 excluded by screening; 246 excluded; 58 studies evaluated)

 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Four reviewers worked in pairs and independently determined study eligibility. Data on study characteristics, study quality, and outcomes were extracted by one reviewer and checked for accuracy by another. Published and unpublished literature were used. 

FINAL NUMBER STUDIES INCLUDED = 37 

 

TOTAL PATIENTS INCLUDED IN REVIEW = 10,581

 

SAMPLE RANGE ACROSS STUDIES = 45–1,379

 

KEY SAMPLE CHARACTERISTICS: Solid and hematologic malignancies; primarily receiving chemotherapy; primarily advanced disease; other demographics (e.g., age, gender, ethnicity) not stated

ESAs provide a small but clinically important improvement in anaemia-related symptoms (Functional Assessment of Cancer Therapy–Anemia [FACT-An]), which was confirmed when the analysis was restricted to placebo-controlled RCTs in patients receiving chemotherapy. For fatigue-related symptoms (Functional Assessment of Cancer Therapy–Fatigue [FACT-F]), the overall effect did not reach the threshold for a clinically important difference (CID). For FACT-F, there was some evidence that treatment effects were above the threshold for a CID in RCTs in patients receiving chemotherapy with hemoglobin levels below 12 g/dl–1 at baseline and in RCTs stopping ESAs at hemoglobin levels above 13 g/dl–1.

 

However, these findings for FACT-F were not confirmed when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy.