Adding erythropoietin (EPO) did not improve local-regional control for anemic patients with head and neck squamous cell carcinoma (HNSCC) who receive radiation therapy or chemoradiation. These long-term analysis results from the Radiation Therapy Oncology Group (RTOG) 9903 study were published in the International Journal of Radiation Oncology * Biology * Physics (2015; doi:10.1016/j.ijrobp.2014.12.018).
RTOG 9903, an open-label, phase 3 randomized trial, examined if the addition of EPO, which stimulates the body’s bone marrow to increase red blood cell production to prevent and to treat anemia, to radiation therapy would improve disease control in anemic patients with HNSCC. The study accrued 148 patients from June 2000 to November 19, 2003, and 54 cancer centers participated in the trial.
Of the 141 patients included in the study, 69 were randomized to receive radiation therapy or chemotherapy plus radiation, and 72 were randomized to receive radiation therapy or chemotherapy plus radiation with EPO.
For this long-term analysis, the median follow-up for surviving patients was 7.95 years (range 1.66 to 10.08 years) and 3.33 years for all patients (range 0.03 to 10.08 years).
This new analysis of RTOG 9903 found that at five-year follow-up, the local-regional failure rate was 39.4% for patients who received radiation therapy or chemoradiation without EPO and 46.2% for patients who received EPO (hazard ratio [HR] 1.27 on univariate analysis and 1.40 on multivariate analysis).
The 5-year local-regional progression-free survival rate was 37.6% for patients who did not receive EPO and 31.5% for patients who received EPO (HR 1.28 on univariate analysis and 1.39 on multivariate analysis).
The 5-year overall survival rate was 38.2% for patients who did not receive EPO and 36.9% for patients who received EPO (HR 1.13 on univariate analysis and 1.23 on multivariate analysis). The 5-year distant metastases rate was 14.5% for patients who did not receive EPO and 15.6% for patients who received EPO (HR 1.03 on univariate analysis and 1.07 on multivariate analysis).
None of the differences were statistically significant; however, the HR in this long-term follow-up demonstrated improved outcomes for the patients who did not receive EPO.
“It is well-known that cancer patients with anemia (low hemoglobin) have lower cure rates than patients with normal hemoglobin levels. RTOG 9903 was aimed at improving the outcomes of anemic patients with head and neck squamous cell carcinoma by restoring their hemoglobin levels to normal,” said George Shenouda, MD, lead author of the study and an associate professor of oncology and otolaryngology at McGill University Health Centre in Montreal, Quebec, Canada.
“The initial analysis of the results was unexpected and led to the study’s early closure because of a possible detrimental effect of EPO. While EPO improved hemoglobin levels, the control rates were not similarly improved. This long-term analysis confirms that EPO is not the appropriate treatment option for our anemic HNSCC patients. It is important for us to be aware that EPO is a growth factor and as such, may stimulate the growth of cancer cells, resulting in decreased tumor control.”