Can Erythropoietin Therapy Improve Survival?

Abstract

The presence of anaemia in patients with cancer is correlated with poor clinical outcome, a reduced tumour response to anticancer therapy and an increased risk of mortality. This observation has led to speculation as to whether treatment of anaemia can enhance survival rates. The majority of studies have suggested that erythropoietic therapy either does not change or improves disease-free and/or overall survival. Only two studies, one in breast cancer and the other in head and neck cancer, both of which used epoetin outside its approved indications, have observed a decrease in survival in epoetin-treated patients compared with controls. Methodological issues and baseline imbalances between groups in prognostic factors for survival that may have favoured placebo treatment have complicated the interpretation of these studies. In contrast, a Cochrane meta-analysis of randomised, controlled trials of epoetin in anaemic patients with cancer that reported survival identified 19 trials up to the end of 2001 with 2,865 patients. This meta-analysis reported a hazard ratio for overall survival of 0.81 (95% CI 0.67–0.99) for adjusted data and a hazard ratio of 0.84 (95% CI 0.69–1.02) for unadjusted data. A recent meta-analysis of nine randomised, controlled trials of epoetin beta (n = 1,413) suggests that use of this therapy is associated with a reduced risk of tumour progression. This meta-analysis also showed that no association existed between the risk of overall mortality or thromboembolic mortality and epoetin beta therapy. These results suggest that treatment of anaemic patients with cancer with epoetin beta is effective and safe.

Recombinant Human Erythropoietin Is Associated with Increased Overall Survival in Patients with Multiple Myeloma

“…Although these studies did not note a survival difference among patients who did and those who did not receive rhEPO, they involved only a short course of treatment with rhEPO (often around 12 weeks), were not designed and powered to assess overall survival, and often resulted in the controls receiving rhEPO after the study was terminated, thus clouding a possible effect on overall survival [11]. A meta-analysis of randomized controlled trials of the use of rhEPO for anemia associated with cancer and cancer treatment noted an overall survival benefit for the use of rhEPO (adjusted hazard ratio = 0.81; 95% CI = 0.67–0.99) [12, 13]. However, the same authors recently published a meta-analysis which included 57 studies and over 9,000 patients [14].…”

Expression and function of erythropoietin receptors in tumors

“…In those trials, decreased survival and increased tumor progression were observed in patients who received epoetin α or epoetin β compared with patients who received placebo. These outcomes were in contrast to many clinical trials, which demonstrated that erythropoiesis‐stimulating agents (ESAs) are safe and efficacious for the treatment of anemia in cancer patients 3, 4. These trials were criticized for poor study design and execution 4.…”

Erythropoiesestimulierende Substanzen: günstiges Sicherheitsprofil bei indikationskonformer Anwendung

“…From these data, it is concluded that in clinically and statistically well-designed studies, ESA therapy has no adverse effects on survival [55]. It produces the expected increase in Hb levels and hence lowers transfusion frequency.…”