Abstract
Background: Epoetin (EPO), darbepoetin (DARB) and red blood cell transfusions (RBCT) are therapeutic alternatives to treat anemia associated with cancer and cancer therapy. Results of randomized controlled trials (RCTs) conflict, and some question the safety of EPO and DARB. Previously, we systematically reviewed this topic (Bohlius et al, JNCI 2005). Since then many new studies became available necessitating an update the prior systematic review.
Objectives: To determine the effectiveness and safety of recombinant human erythropoietin and darbepoetin to prevent or alleviate anemia in cancer patients (pts), and to compare current and previous results of systematic review.
Methods: Included RCTs compared EPO or DARB plus RBCT if needed with observation plus RBCT for prophylaxis or treatment of anemia in cancer patients receiving or not receiving antineoplastic therapy. Patients had solid tumors or hematological malignancies including MDS. Endpoints were rates of RBCT, hematological response (defined as transfusion free Hb increase of 2 g/dL), tumor response, overall survival and thrombo embolic events. Medical databases (Cochrane Library, MEDLINE, EMBASE) and conference proceedings were searched (first review:1985–2001, update up to 04/2005). We included full-text and abstract publications plus unpublished data. Data extraction and quality assessment were in duplicate.
Results: The update included 57 trials with 9,353 patients. Use of EPO or DARB significantly reduced the relative risk (RR) of RBCTs (RR 0.64; 95%-CI 0.60–0.68; 42 trials, n = 6,510). On average, participants in the EPO/DARB groups received one unit of blood less than controls (weighted mean difference −1.05; 95% CI− 1.32 −0.78; 14 trials, n = 2,353). Hb response (baseline Hb < 12 g/dL) was more likely in the EPO/DARB group (RR 3.43; 95%-CI 3.07–3.84; 22 trials, n = 4,307). Thrombo embolic complications were more frequent in patients receiving EPO/DARB: RR 1.67 (95%-CI 1.35–2.06; 35 trials, n = 6,769). Uncertainties remain whether and how EPO/DARB affects tumor response (fixed effect RR 1.12; 95%-CI 1.01–1.23; random effects: RR 1.09; 95%-CI 0.94–1.26; 13 trials, n = 2,833) or overall survival (HR 1.08; 95%-CI 0.99–1.18; 42 trials, n = 8,167). Subgroup analyses comparing EPO and DARB did not identify clinically or statistically significant differences. This update confirms previous findings for transfusion rates and hematological response. In contrast, the update suggests EPO/DARB may reduce survival whereas the first review suggested possible benefits (HR 0.81; 95%-CI 0.67–0.99; 19 trials, n = 2,865). Factors possibly contributing to these conflicting results include mortality due to thrombo embolic complications and tumor progression but also methodological limitations such as baseline imbalances.
Conclusion: EPO or DARB given to cancer pts reduces the relative risk for red blood cell transfusion and increases likelihood of hematological response. However, EPO/DARB also increases the risk of thrombo embolic complications. The impact on tumor response and survival is uncertain.
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