Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients.

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis.

BACKGROUND: Anemia associated with cancer and cancer therapy is an important clinical and economic factor in the treatment of malignant diseases. METHODS: We conducted a systematic literature review to assess the efficacy of erythropoietin to prevent or treat anemia in cancer patients with regard to red blood cell transfusions, hematologic response, adverse events, and overall survival. We searched the Cochrane Library, Medline, EMBASE, and other databases for relevant articles published from January 1985 to December 2001. We included all randomized controlled trials that compared the use of recombinant human erythropoietin (plus transfusion, if needed) with no erythropoietin treatment (plus transfusion, if needed). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated under a fixed-effects model. Clinical and statistical heterogeneity were examined with sensitivity analyses and meta-regression. Statistical tests for effect estimates were two-sided. RESULTS: We identified 27 trials involving 3287 adult patients. Patients treated with erythropoietin had a lower relative risk of having a blood transfusion than untreated patients (RR = 0.67, 95% CI = 0.62 to 0.73). Erythropoietin-treated patients with baseline hemoglobin levels lower than 10 g/dL were more likely to have a hematologic response than untreated patients (RR = 3.60, 95% CI = 3.07 to 4.23). The relative risk for thromboembolic complications after erythropoietin treatment was not statistically significantly increased (RR = 1.58, 95% CI = 0.94 to 2.66) compared with that of untreated patients. There is suggestive but inconclusive evidence that erythropoietin may improve overall survival (adjusted data: hazard ratio [HR] = 0.81, 95% CI = 0.67 to 0.99; unadjusted data: HR = 0.84, 95% CI = 0.69 to 1.02). CONCLUSIONS: Erythropoietin treatment may reduce the risk for blood transfusions and improve hematologic response in cancer patients. However, our favorable survival outcome is in contrast to two large (N = 351 and 939) recently published randomized controlled trials in which erythropoietin-treated patients had statistically significantly worse survival than untreated patients. Possible reasons for the disparity with our results include differences in study population and design, higher target hemoglobin levels and higher risk of thromboembolic complications, and concerns that erythropoietin may stimulate tumor growth.

Effectiveness of erythropoietin in the treatment of patients with malignancies: methods and preliminary results of a Cochrane review.

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.