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

Jens Overgaard; Camilla Molich Hoff; Hanne Sand Hansen; Lena Specht; Marie Overgaard; Pernille Lassen; Elo Andersen; Jørgen Johansen; Lisbeth Juhler Andersen; Jan Folkvard Evensen; Jan Alsner; Cai Grau

doi:10.1016/j.radonc.2018.02.018

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

Jens Overgaard, Camilla Molich Hoff, Hanne Sand Hansen, Lena Specht, Marie Overgaard, Pernille Lassen, Elo Andersen, Jørgen Johansen, Lisbeth Juhler Andersen, Jan Folkvard Evensen, Jan Alsner, Cai Grau

Institut for Klinisk Medicin

17 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Radiotherapy & Oncology
Vol/bind	127
Udgave nummer	1
Sider (fra-til)	12-19
ISSN	0167-8140
DOI	https://doi.org/10.1016/j.radonc.2018.02.018
Status	Udgivet - apr. 2018

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Citationsformater

Overgaard, J., Hoff, C. M., Hansen, H. S., Specht, L., Overgaard, M., Lassen, P., Andersen, E., Johansen, J., Andersen, L. J., Evensen, J. F., Alsner, J., & Grau, C. (2018). 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. Radiotherapy & Oncology, 127(1), 12-19. https://doi.org/10.1016/j.radonc.2018.02.018

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 et al.

I: Radiotherapy & Oncology, Bind 127, Nr. 1, 04.2018, s. 12-19.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Overgaard, J, Hoff, CM, Hansen, HS, Specht, L, Overgaard, M, Lassen, P, Andersen, E, Johansen, J, Andersen, LJ, Evensen, JF, Alsner, J & Grau, C 2018, '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', Radiotherapy & Oncology, bind 127, nr. 1, s. 12-19. https://doi.org/10.1016/j.radonc.2018.02.018

Overgaard J, Hoff CM, Hansen HS, Specht L, Overgaard M, Lassen P et al. 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. Radiotherapy & Oncology. 2018 apr.;127(1):12-19. doi: 10.1016/j.radonc.2018.02.018

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title = "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",

abstract = "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.",

keywords = "Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell/drug therapy, Darbepoetin alfa/therapeutic use, Disease-Free Survival, Dose Fractionation, Radiation, Female, Head and Neck Neoplasms/drug therapy, Hemoglobins/metabolism, Humans, Male, Middle Aged, Nimorazole/administration & dosage, Oxygen/metabolism, Patient Compliance, Radiation-Sensitizing Agents/administration & dosage, Squamous Cell Carcinoma of Head and Neck",

author = "Jens Overgaard and Hoff, {Camilla Molich} and Hansen, {Hanne Sand} and Lena Specht and Marie Overgaard and Pernille Lassen and Elo Andersen and J{\o}rgen Johansen and Andersen, {Lisbeth Juhler} and Evensen, {Jan Folkvard} and Jan Alsner and Cai Grau",

year = "2018",

month = apr,

doi = "10.1016/j.radonc.2018.02.018",

language = "English",

volume = "127",

pages = "12--19",

journal = "Radiotherapy & Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

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

PY - 2018/4

Y1 - 2018/4

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

SN - 0167-8140

VL - 127

SP - 12

EP - 19

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

IS - 1

ER -