Anemia correction in malignancy management: threat or opportunity?

OBJECTIVES: The presence of anemia and/or hypoxia in cancer patients have both been correlated with worse outcomes. While some retrospective data suggest an improvement in outcomes in cervical cancer patients whose anemia has been corrected, the critical level to which hemoglobin should be raised and the issue of whether raising hemoglobin translates into a survival advantage remain controversial. This debate has more recently expanded to concerns over how we raise hemoglobin, with 2 recent randomized trials suggesting impaired survival outcomes in the groups who received poietic proteins to correct hemoglobin levels to normal and above values.
METHODS: A comprehensive literature search was performed utilizing combinations of the key search words anemia, hypoxia, radiotherapy, HIF-1alpha, angiogenesis, and erythropoietin.
RESULTS: The preponderance of evidence suggest a correlation between both anemia and worse outcome as well as hypoxia and worse outcome; however the relationship between anemia and hypoxia remains complex. A critical review of molecular changes associated with hypoxia that drive the molecular process, anemia correction and the data on the use of poietic proteins, and a review of future directions of research which focus on the opportunity of therapies correcting hypoxia or hypoxia-relevant targets is also presented.
CONCLUSIONS: Anemia and hypoxia remain biologically plausible targets for improving therapy. The potential benefit of raising hemoglobin will depend on whether anemia can influence treatment resistance and whether anemia plays a reversible role in driving the molecular milieu contributing to malignant clonogen survival and dissemination.