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% Cl = 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.