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Summarized by: Catherine Cunningham & Kevin O’Donnell, Fall 2007

One of the major obstacles encountered by drug manufactures developing cancer therapies is the inability to specifically target cancer cells without effecting normal cellular function.  Most drugs currently in use exert their effects by inhibiting various pathways crucial to cell cycling and growth.  In this way, these drugs inhibit tumor growth. The cancer drugs affect normal tissues that rely on continuous cellular renewal, which is the basis for major side effects. These include hair, gut and bone marrow progenitors also inhibited as a side-effect. These inhibitory side effects give rise to the well recognized presentation of hair loss, anemia, and immunosuppression in a patient undergoing chemotherapy.

Erythropoietin is a growth factor, with functions on erythropoiesis, which is represented as the generation of red blood cells. It is used in conjunction with other cancer treatments to counteract the side effects associated with these therapies, specifically anemia induced by chemotherapy.  Anemia is often used as a prognostic tool in oncology since studies have shown its occurrence to increase the risk of death in various types of cancers. Consequently, it was hypothesized that erythropoietin could possibly impart some type of survival benefit to cancer patients. Despite direct evidence to the contrary, erythropoietin is still one of the most widely prescribed drugs in cancer treatment today. 
Blau raises the issue of whether erythropoietin drugs are actually safe when used for their FDA-approved indication – treatment of chemotherapy-induced anemia. The original clinical trials did not require any assessment of survival benefit because erythropoietin was only considered a complimentary therapy.  However, a number of recent Phase II and III trials that sought to broaden the scope of FDA approval were prematurely terminated because of a statistically significant worsening of survival of erythropoietin-treated patients. 

He suggests that this decrease in survival may be attributed to the presence of erythropoietin receptors aberrantly located on cells comprising the tumor.  In fact, he has preliminary data suggesting patients with erythropoietin receptors on the tumor do have a decrease in survival while those without the receptors on the tumor may have some benefit from erythropoietin treatment.  Therefore, as a protective measure for the patient population receiving erythropoietin therapy, he would like to retrospectively analyze the tumor biopsies from the previous trials, looking for the presence or absence of erythropoietin receptors, and correlate this data with survival benefit.

The central issue addressed by Blau about determining what is the safe usage of adjuvant erythropoietin administration during chemotherapy is valid and important.  He stresses that our knowledge of how erythropoietin interacts with it’s receptor located on a tumor is cursory at best and needs to be elucidated before we can justify administering the drug as ancillary treatment.  In reality, erythropoietin therapy may only be indicated in a specific subset of patients with characteristic tumor markers, a finding which would change the current paradigm of treatment.

Note: A potential conflict of interest exists in that the author of this article is the co-founder and a stockholder of CellNexus, a pharmaceutical company that manufactures a drug which could be considered the direct competitor of erythropoietin. 

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