Tumor progression associated with erythropoiesis-stimulating agents

Area of Science:

• Oncology
• Hematology
• Clinical Trials

Background:

• Erythropoiesis-stimulating agents (ESAs) are used to treat anemia, particularly chemotherapy-induced anemia.
• Concerns have been raised regarding the potential for ESAs to increase tumor progression in cancer patients.
• The U.S. Food and Drug Administration (FDA) has issued black box warnings and labeling changes related to this risk.

Purpose of the Study:

• To evaluate and critique clinical trials that reported increased tumor progression in cancer patients receiving ESAs.
• To characterize and compare findings from studies leading to FDA regulatory actions.
• To assess the evidence for ESAs influencing cancer disease progression.

Main Methods:

• Literature search of MEDLINE and PubMed (1950-2008) using terms related to ESAs, anemia, and cancer progression.
• Review of MedWatch alerts, FDA advisory committee briefs, and bibliographies.
• Inclusion of English-language studies suggesting increased tumor progression or death with ESA use.

Main Results:

• Ten trials investigating off-label ESA use in cancer patients reported increased tumor progression or treatment-associated death.
• Two trials showed worse overall survival with ESAs compared to placebo.
• Many studies had limitations including imbalanced groups and poor design; none were powered to detect worse outcomes.

Conclusions:

• Additional well-designed trials focusing on safety outcomes are ongoing to quantify the risk of tumor progression with ESAs.
• Until definitive results are available, ESAs should be used strictly according to FDA-approved labeling.
• The potential risk of tumor progression with ESAs requires careful consideration in clinical practice.