If Only It Were Simple

Fatigue is one of the most common and most bothersome symptoms experienced by cancer patients, with chemotherapy-induced anemia one of the major causes. Erythropoietic therapy corrects anemia, and because improved quality of life1 and functional status2 have been shown as a result of improved hemoglobin levels, treatment with these stimulating agents is warranted. In reality, however, biologic systems are not that simple. If the effect of erythropoietin and darbopoietin was solely limited to raising hemoglobin levels, current clinical trials would have answered most of the searing questions and unqualified recommendations for usage could be made with a comfortable degree of certitude. However, the biologic end-point of raising hemoglobin to 12 to 14 g/dL has other impacts on vascular and hematologic systems, with possible rheologic consequences leading to an increased risk of thrombovascular events. Of concern is the possibility that raising hemoglobin levels adversely affects survival. A decrease in survival for erythropoietin-treated patients was noted in 2 randomized trials: one in head and neck cancer and one in metastatic breast cancer.3 In both of these trials, the incidence of serious thrombotic events was greater in the treatment arms. Probably, one of the few certainties in medicine is that one trial can never answer all the questions. Even more basically, the perfect trial design—one that does not lead to post-hoc alternative interpretation or raise further questions—probably cannot be achieved. Human biology is complex and the factors that must be considered are myriad. Leyland Jones et al.3 discussed the possibility that raising hemoglobin...

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Rodger J. Winn is the Editor-in-Chief of JNCCN. He is Clinical Consultant at the National Quality Forum, and his past positions include Associate Professor of Clinical Medicine at The University of Texas M. D. Anderson Cancer Center. Dr. Winn received his medical degree from Jefferson Medical College of Philadelphia. His postgraduate training includes an internship and residency at Jefferson Medical College, and he also completed a medical oncology fellowship at Memorial Sloan-Kettering Cancer Center in New York. He is board certified in internal medicine and holds subspecialty certification in oncology.
  • 1

    LittlewoodTJBajettaENortierJW. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving non-platinum chemotherapy: Results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol2001;19:2865-2874.

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  • 2

    BerndtEKallichJMcDermottA. Reductions in anaemia and fatigue are associated with improvements in productivity in cancer patients receiving chemotherapy. Pharmacoeconomics2005;23:505-514.

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  • 3

    Leyland-JonesBSemiglazovVPawlickiM. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: A survival study. J Clin Oncol2005;23:5960-5972.

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  • 4

    BohliusJLangensiepenSSchwarzerG. Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis. J Nat Cancer Inst2005;97:489-498.

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  • 5

    SteensmaDPLoprinziCL. Erythropoietin use in cancer patients: a matter of life and death?J Clin Oncol2005;23:5865-5868.

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