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Preliminary Study IDs Genetic Biomarkers Linking Erythropoietin to Cancer Growth

CHICAGO (GenomeWeb News) — An increasing body of evidence is showing that erythropoietin, the widely used hematopoietic drug used to counter the anemia caused by most chemotherapies, may also encourage cancer cells themselves to grow in certain malignancies.
 
Yet despite this evidence, many oncologists continue to prescribe the drug because they believe its risks do not outweigh its benefits — among them avoiding blood transfusions and treatment discontinuation — and because it has been impossible to uncover which patients in whom EPO might spur cancer growth.
 
Now, a team of researchers from Washington University claims that a pair of biomarkers can help identify patients with head and neck cancer in whom EPO may do more harm than good.
 
Anthony Blau, adjunct associate professor of genome sciences, has found that testing levels of erythropoietin receptor mRNA in tumor tissue from these patients “may predict whether patients will experience tumor progression after taking” EPO.
 
Blau, who is also associate professor of medicine and hematology at WashU, presented the results of this study here this week at the annual meeting of the American Society of Clinical Oncology.
 
To arrive at their results, Blau and his colleagues measured EpoR mRNA levels in 101 archived tumor samples from patients who had previously participated in a Phase III trial studying the effects of adjuvant EPO and radiation therapy for head and neck cancer. The patients were randomized into groups receiving radiation plus EPO or radiation plus placebo.
 
For the subset of patients treated with radiation alone and who had not undergone surgery, the researchers found that tumors with high levels of EpoR mRNA progressed faster in patients who received erythropoietin than in those who received a placebo.
 
The team found similar results among patients whose tumor showed high mRNA levels of Janus Kinase 2, or Jak2, which is known to be the primary transmitter of EpoR signals in red blood cells.
 
During his presentation, Blau stressed that his group’s findings are preliminary until they are validated by using tumor samples from patients in other Phase III trials of EPO.
 
“The definitive answer to this question lies locked in the files of pathologists’ offices,” he said.
 
It is difficult to estimate the use of EPO in cancer patients because the drug has been around since the 1980s and has many generic versions. But one drug maker’s revenue from the drug shows how important it can be to at least its top line: Amgen sold around $4.1 billion of its EPO Aranesp in 2006, which accounted for almost one-third of the company's $14.3 billion in total receipts that year.
 
On March 7, Amgen released a Dear Doctor letter alerting that on Nov. 8, 2007, Aranesp’s label was revised, including having a Black Box Warning added, to reflect that six studies showed “increased mortality and more rapid tumor progression in patients with cancer receiving” erythropoietin-stimulating agents.
 
The revised label now states that ESAs “shortened overall survival and/or time to tumor progression in clinical studies in patients with advanced breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of ≥ 12 g/dL.”
 
On March 18, the US Food and Drug Administration oncology subcommittee issued a briefing in which it said that “there are no studies which clearly establish the effect of ESAs on survival or on tumor promotion when ESAs were administered in accordance with recommended dose in product labeling across multiple cancer subtypes.”
 

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