DAHANCA 10: Effect of darbepoetin alfa and radiotherapy in the treatment of squamous cell carcinoma of the head and neck. A multicenter, open-label, randomized, phase 3 trial by the Danish head and neck cancer group
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DAHANCA 10 : Effect of darbepoetin alfa and radiotherapy in the treatment of squamous cell carcinoma of the head and neck. A multicenter, open-label, randomized, phase 3 trial by the Danish head and neck cancer group. / Overgaard, Jens; Hoff, Camilla Molich; Hansen, Hanne Sand; Specht, Lena; Overgaard, Marie; Lassen, Pernille; Andersen, Elo; Johansen, Jørgen; Andersen, Lisbeth Juhler; Evensen, Jan Folkvard; Alsner, Jan; Grau, Cai.
I: Radiotherapy & Oncology, Bind 127, Nr. 1, 2018, s. 12-19.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - DAHANCA 10
T2 - Effect of darbepoetin alfa and radiotherapy in the treatment of squamous cell carcinoma of the head and neck. A multicenter, open-label, randomized, phase 3 trial by the Danish head and neck cancer group
AU - Overgaard, Jens
AU - Hoff, Camilla Molich
AU - Hansen, Hanne Sand
AU - Specht, Lena
AU - Overgaard, Marie
AU - Lassen, Pernille
AU - Andersen, Elo
AU - Johansen, Jørgen
AU - Andersen, Lisbeth Juhler
AU - Evensen, Jan Folkvard
AU - Alsner, Jan
AU - Grau, Cai
N1 - Copyright © 2018 Elsevier B.V. All rights reserved.
PY - 2018
Y1 - 2018
N2 - PURPOSE: To evaluate if correction of low hemoglobin (Hb) levels by means of darbepoetin alfa improves the outcomes of radiotherapy in patients with squamous cell carcinoma of the head and neck (HNSCC).PATIENTS AND METHODS: Patients eligible for primary radiotherapy and who had Hb values below 14.0 g/dl were randomized to receive accelerated fractionated radiotherapy with or without darbepoetin alfa. Patients also received the hypoxic radiosensitizer nimorazole. Darbepoetin alfa was given weekly during radiotherapy or until the Hb value exceeded 15.5 g/dl.RESULTS: Following a planned interim analysis which showed inferiority of the experimental treatment the trial was stopped after inclusion of 522 patients (of a planned intake of 600). Of these, 513 were eligible for analysis (254 patients treated with darbepoetin alfa and 259 patients in the control group). Overall, the patients were distributed according to the stratification parameters (gender, T and N staging, tumor site). Treatment with darbepoetin alfa increased the Hb level to the planned value in 81% of the patients. The compliance was good without excess serious adverse events. The results showed a poorer outcome with a 5-year cumulative loco-regional failure rate of 47% vs. 34%, Hazard Ratio (HR): 1.53 [1.16-2.02], for the darbepoetin alfa vs. control arm, respectively. This was also seen for the endpoints of event-free survival (HR: 1.36 [1.09-1.69]), disease-specific death (HR: 1.43 [1.08-1.90]), and overall survival (HR: 1.30 [1.02-1.64]). There was no enhanced risk of cardio-vascular events observed in the experimental arm or any significant differences in acute or late radiation related morbidity. All univariate analyses were confirmed in a multivariate setting.CONCLUSION: Correction of the Hb level with darbepoetin alfa during radiotherapy of patients with HNSCC resulted in a significantly poorer tumor control and survival.
AB - PURPOSE: To evaluate if correction of low hemoglobin (Hb) levels by means of darbepoetin alfa improves the outcomes of radiotherapy in patients with squamous cell carcinoma of the head and neck (HNSCC).PATIENTS AND METHODS: Patients eligible for primary radiotherapy and who had Hb values below 14.0 g/dl were randomized to receive accelerated fractionated radiotherapy with or without darbepoetin alfa. Patients also received the hypoxic radiosensitizer nimorazole. Darbepoetin alfa was given weekly during radiotherapy or until the Hb value exceeded 15.5 g/dl.RESULTS: Following a planned interim analysis which showed inferiority of the experimental treatment the trial was stopped after inclusion of 522 patients (of a planned intake of 600). Of these, 513 were eligible for analysis (254 patients treated with darbepoetin alfa and 259 patients in the control group). Overall, the patients were distributed according to the stratification parameters (gender, T and N staging, tumor site). Treatment with darbepoetin alfa increased the Hb level to the planned value in 81% of the patients. The compliance was good without excess serious adverse events. The results showed a poorer outcome with a 5-year cumulative loco-regional failure rate of 47% vs. 34%, Hazard Ratio (HR): 1.53 [1.16-2.02], for the darbepoetin alfa vs. control arm, respectively. This was also seen for the endpoints of event-free survival (HR: 1.36 [1.09-1.69]), disease-specific death (HR: 1.43 [1.08-1.90]), and overall survival (HR: 1.30 [1.02-1.64]). There was no enhanced risk of cardio-vascular events observed in the experimental arm or any significant differences in acute or late radiation related morbidity. All univariate analyses were confirmed in a multivariate setting.CONCLUSION: Correction of the Hb level with darbepoetin alfa during radiotherapy of patients with HNSCC resulted in a significantly poorer tumor control and survival.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Squamous Cell/drug therapy
KW - Darbepoetin alfa/therapeutic use
KW - Disease-Free Survival
KW - Dose Fractionation, Radiation
KW - Female
KW - Head and Neck Neoplasms/drug therapy
KW - Hemoglobins/metabolism
KW - Humans
KW - Male
KW - Middle Aged
KW - Nimorazole/administration & dosage
KW - Oxygen/metabolism
KW - Patient Compliance
KW - Radiation-Sensitizing Agents/administration & dosage
KW - Squamous Cell Carcinoma of Head and Neck
U2 - 10.1016/j.radonc.2018.02.018
DO - 10.1016/j.radonc.2018.02.018
M3 - Journal article
C2 - 29523409
VL - 127
SP - 12
EP - 19
JO - Radiotherapy & Oncology
JF - Radiotherapy & Oncology
SN - 0167-8140
IS - 1
ER -
ID: 213153854