The safety of erythropoietin stimulating agents in surgical patients with head and neck squamous cell carcinoma—a narrative review

Abstract

Objective: To determine whether the use of erythropoietin stimulating agents (ESAs) in patients with head and neck squamous cell carcinoma (HNSCC) undergoing surgical management is contraindicated. Background: ESAs are commonly used adjuncts for anaemia management in select patient populations. HNSCC patients can be vulnerable to multifactorial anaemia, and it is commonly identified as a modifiable risk factor preoperatively. Anaemia contributes to tumour hypoxia which influences the degree of treatment resistance. Strong evidence linking anaemia with poorer locoregional control and overall survival in HNSCC has led researchers to pursue therapies which may improve haemoglobin levels. Despite correcting haemoglobin levels, the use of ESAs in HNSCC patients has failed to demonstrate an improvement in disease free survival or overall survival. Research in HNSCC patients undergoing primary radiotherapy demonstrates clear trends towards increased rates of locoregional failure and mortality, though research in surgical patients is lacking. Methods: A narrative review was conducted of research in the English language with no date range limitation. A search was conducted of PubMed and CINAHL databases using the following MeSH terms: “erythropoietin”, “squamous cell carcinoma”, “squamous cell carcinoma of head and neck”, “HNSCC”, “epoetin” and “surgery”. Results: Studies in patients with HNSCC receiving ESA therapy during primary curative intent surgical management was limited. A total of 457 studies were identified, from this there were no studies reporting outcomes in patients treated with primary surgical management alone. From studies of HNSCC patients receiving radiotherapy as primary or adjuvant therapy, the use of ESAs was associated with increased risk of locoregional recurrence and mortality. Conclusions: Despite a lack of research investigating surgical cohorts with HNSCC, the clear trend towards early locoregional failure and mortality amongst patients with advanced HNSCC receiving primary curative-intent radiotherapy on ESA therapy is suggestive of their relative contraindication. Several good quality randomised controlled trials have detected significant differences in rates of locoregional recurrence and overall survival. These studies and the issuing of a black box warning by the FDA should alert clinicians to this risk. Future research aimed at stratifying the risk for surgical patients may be of benefit in early disease when the risks are less well documented.

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