title: Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).
  
  
  METHODS
  The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm.
  
  
  RESULTS
  A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.
  
  
  CONCLUSIONS
  This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.
authors: McGill University, Montreal, Quebec, Canada. Electronic address: George.shenouda@muhc.mcgill.ca.
authors: George
authors: G
authors: Shenouda
authors: NRG Oncology Statistics and Data Management Center.
authors: Qiang
authors: Q
authors: Zhang
authors: University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: K Kian
authors: KK
authors: Ang
authors: University Hospitals of Cleveland, Cleveland, Ohio.
authors: Mitchell
authors: M
authors: Machtay
authors: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors: Matthew B
authors: MB
authors: Parliament
authors: University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
authors: Diane
authors: D
authors: Hershock
authors: University of Maryland Medical System, Baltimore, Maryland.
authors: Mohan
authors: M
authors: Suntharalingam
authors: University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
authors: Alexander
authors: A
authors: Lin
authors: Brooklyn Minority-based Community Clinical Oncology Program, State University of New York Downstate Medical Center, Brooklyn, New York.
authors: Marvin
authors: M
authors: Rotman
authors: Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke (Québec), Québec, Canada.
authors: Abdenour
authors: A
authors: Nabid
authors: Akron City Hospital, Akron, Ohio.
authors: Susan
authors: S
authors: Hong
authors: Northeastern Ontario Regional Cancer Centre, Sudbury, Ontario, Canada.
authors: Sarwat
authors: S
authors: Shehata
authors: Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Anthony J
authors: AJ
authors: Cmelak
authors: McGill University, Montreal, Quebec, Canada.
authors: Khalil
authors: K
authors: Sultanem
authors: Stanford University Medical Center, Stanford, California.
authors: Quynh-Thu
authors: QT
authors: Le
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006441:Hemoglobin A / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D006441:Hemoglobin A