Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial.
BACKGROUND
Anaemia is associated with poor cancer control, particularly in patients undergoing radiotherapy. We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer.


METHODS
We did a multicentre, double-blind, randomised, placebo-controlled trial in 351 patients (haemoglobin <120 g/L in women or <130 g/L in men) with carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received curative radiotherapy at 60 Gy for completely (R0) and histologically incomplete (R1) resected disease, or 70 Gy for macroscopically incompletely resected (R2) advanced disease (T3, T4, or nodal involvement) or for primary definitive treatment. All patients were assigned to subcutaneous placebo (n=171) or epoetin beta 300 IU/kg (n=180) three times weekly, from 10-14 days before and continuing throughout radiotherapy. The primary endpoint was locoregional progression-free survival. We assessed also time to locoregional progression and survival. Analysis was by intention to treat.


RESULTS
148 (82%) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L (women) or 150 g/L (men) compared with 26 (15%) given placebo. However, locoregional progression-free survival was poorer with epoetin beta than with placebo (adjusted relative risk 1.62 [95% CI 1.22-2.14]; p=0.0008). For locoregional progression the relative risk was 1.69 (1.16-2.47, p=0.007) and for survival was 1.39 (1.05-1.84, p=0.02).


CONCLUSIONS
Epoetin beta corrects anaemia but does not improve cancer control or survival. Disease control might even be impaired. Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials.
Henke
Michael
M
Abteilung Strahlenheilkunde der Radiologischen Universitätsklinik, Hugstetter Strasse 55, D-79106, Freiburg, Germany. henke@uni-freiburg.de
Laszig
Roland
R
Rübe
Christian
C
Schäfer
Ulrich
U
Haase
Klaus-Dieter
KD
Schilcher
Burkhard
B
Mose
Stephan
S
Beer
Karl T
KT
Burger
Ulrich
U
Dougherty
Chris
C
Frommhold
Hermann
H
D000740:Anemia / Q000188:drug therapy* / Q000453:epidemiology; D024221:Antineoplastic Protocols / Q000592:standards; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000532:radiotherapy*; D015897:Comorbidity; D018572:Disease-Free Survival; D004921:Erythropoietin / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000532:radiotherapy*; D006801:Humans; D016016:Proportional Hazards Models; D018787:Radiation Oncology / Q000592:standards; D011994:Recombinant Proteins; D016896:Treatment Outcome
D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin