Androgen Augmentation of Epoetin
Authors: Harry W. Daniell
Journal: Journal of Clinical Oncology (2003)

Guidelines for the Use of Epoetin: Have Quality-of-Life Benefits Been Proven?To the Editor: In their recent article, Rizzo et al 1 report evidence-based clinical practice guidelines for the use of epoetin.Because the treatment of anemia is a major aspect of cancer care and has received considerable attention particularly in terms of epoetin use, 2 such guidelines are long awaited.Although evidence in randomized trials for effectiveness of epoetin exists in terms of increasing serum hemoglobin and reducing the transfusion rate, in our view, there is far less conclusive evidence in terms of the end point of primary importance: improvement in quality of life (QOL) as assessed by the patients themselves.Rizzo et al 1 question the value of past QOL research in this field.We believe this is correct and that improvement of QOL as a result of epoetin treatment has not been definitively proven.This was recently borne out in our published evidence-based systematic review of 13 published studies examining the effect of epoetin solely on cancer patients' QOL. 3 Although results were in general agreement with the findings of Rizzo et al, we found limited evidence of QOL benefit.Many of the trials in this review suffered from serious methodologic problems; this hampers the drawing of conclusions based on these data.Typically, limitations included use of ad hoc, poorly validated measures, often with no justification for measurement selection.In many trials, the measures were inadequate to assess QOL.Often trials were underpowered and had no control or an inadequate control group.Some of the trials were not placebo controlled.Furthermore, patients were probably aware of their serum hemoglobin levels, and this may have influenced their evaluation of QOL.Few studies examined clinical significance.This is a critical factor, because often QOL results may be statistically significant.However, this may have little or no bearing on patient perception of real improvements.Although more recent trials, such as that of Littlewood et al, 4 help us understand the benefit of epoetin to QOL, even such a robust study suffers limitations, as noted by Rizzo et al. 1 We agree with the guideline authors who claim that undertaking QOL in clinical trials is a complex and difficult task.Often investigators are faced with a variety of challenges that are difficult to overcome. 5 With that said, we have increasingly seen studies that show that QOL data can be collected in clinical trials and can provide invaluable information for clinical decision making. 6,7Therefore, we are in agreement with the recommendations of Rizzo et al. 1 More work must be undertaken to prove the benefit of epoetin on patient QOL.The ideal study on QOL in relation to epoetin should be a large, placebo-controlled trial that tests a predefined hypothesis regarding which dimensions of QOL are expected to be improved.The study should use validated instruments with available data on clinical significance.The amount of missing data should be minimal, and all steps for dealing with missing data should be fully reported.