Epoetins and mortality in patients with cancer

Abstract

The meta-analysis by Julia Bohlius and colleagues (May 2, p 1532) summarises the numerous and heterogeneous randomised controlled trials of erythropoiesis-stimulating agents (ESA) in cancer patients. The fi nding was that ESA agents increase mortality and worsen overall survival. Currently, many oncologists prefer not to use ESA under any circumstances. However, what clinical judgment can follow from a meta-analysis in which the studies assessed did not proceed along the recommended guidelines? Neither the 2002 version nor the 2007 update of the guidelines produced by the American Society of Clinical Oncology and the American Society of Hematology had been followed. Similarly, in none of the trials were ESA agents given for the exact indications recommended by the US Food and Drug Administration. Hence, the target haemoglobin concentration was more than 130 g/L in 75% of patients (ie, higher than that needed to correct anaemia), and the ESA dose was twice the standard recommended dose in one study. If these randomised trials had been testing radiotherapy, chemo therapy, or insulin doses that were 50–100% higher than those recommended (or had used them in disorders for which they were not approved) and adverse events resulted, would the usefulness of appropriate radiotherapy, chemotherapy, or insulin be questioned? This meta-analysis of “off -label” ESA use does not necessarily prove that the previous indications for its use (not analysed in the meta-analysis) were wrong. The appropriateness of ESA use in cancer patients is an unresolved question that merits further research, especially in areas such as correcting severe anaemia (ie, not mid-range anaemia) when radiochemotherapy is used with curative intent in tumours with low metastatic potential, and in combining the use of ESA with prophylactic anticoagulation.