RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Epoetin alfa may help prevent or treat cancer-related anemia. It is not yet known whether radiation therapy is more effective with or without epoetin alfa in treating head and neck cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without epoetin alfa in treating patients who have head and neck cancer.

Condition	Treatment or Intervention	Phase
Oral Cancer Throat Cancer	Drug: epoetin alfa  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of radiotherapy (in terms of local-regional control) with or without epoetin alfa in patients with squamous cell carcinoma of the head and neck.
• Compare the disease-specific and overall survival of patients treated with these regimens.
• Compare the hemoglobin level of these patients during radiotherapy.
• Compare the acute and late toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, site of disease (larynx vs hypopharynx vs oropharynx vs oral cavity), T-classification (T1-2 vs T3-4), N-classification and intent of systematic neck node dissection (N0-1 vs N2-3 without node dissection vs N2-3 with node dissection), hemoglobin level and gender (men with 10-12.5 g/dL vs men with 12.5-14 g/dL vs women with 10-12 g/dL vs women with 12-13.5 g/dL), and type of treatment (EORTC standard vs other vs randomized in other trials). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard radiotherapy 5 days a week and receive concurrent epoetin alfa subcutaneously (SC) once weekly.
• Arm II: Patients undergo radiotherapy as in arm I and receive concurrent placebo SC once weekly. Treatment on both arms continues for 6-8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3-6 weeks and 9-14 weeks, every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter. After any locoregional recurrence, patients are followed every 6 months for 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oral cavity, larynx, oropharynx, or hypopharynx
• Stage T1-T4, any N
• No T1, N0 glottic tumor
• No nodal disease from unknown primary
• Previously untreated disease
• No distant metastases
• Planned radiotherapy

PATIENT CHARACTERISTICS: Age:

• 18 to 75

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin greater than 10 g/dL but no greater than 14 g/dL for men
• Hemoglobin greater than 10 g/dL but no greater than 13.5 g/dL for women

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No hypertension (diastolic pressure greater than 100 mmHg) refractory to treatment
• No symptomatic cardiovascular disease
• No deep vein thrombosis

Other:

• No other malignancy except cured basal cell skin cancer or carcinoma in situ of the cervix
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• No smoking during study
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior neoadjuvant chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to head and neck area
• No concurrent nonconventional radiotherapy

Surgery:

• No prior therapeutic surgery to head and neck area

Australia, New South Wales
      Newcastle Mater Misericordiae Hospital, Newcastle,  New South Wales,  NSW 2310,  Australia
Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Clinique Sainte Elisabeth, Namur,  5000,  Belgium
      Cliniques Universitaires Saint-Luc, Brussels (Bruxelles),  1200,  Belgium
      Hopital de Jolimont, Haine-Saint-Paul,  7100,  Belgium
      Institut Jules Bordet, Brussels (Bruxelles),  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Germany
      Universitaetsklinikum Charite, Berlin,  D-10117,  Germany
Hungary
      Radius Hungaricus Oncology Group, Torokbalint,  H-2045,  Hungary
Israel
      Rambam Medical Center, Haifa,  31096,  Israel
Netherlands
      Radiotherapeutisch Instituut Limburg, HEERLEN,  NL-6401 PC,  Netherlands
Spain
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain
Switzerland
      Ospedale San Giovanni, Bellinzona,  CH-6500,  Switzerland
United Kingdom, Scotland
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom

Study chairs or principal investigators

Philippe Lambin, MD,  Study Chair,  Radiotherapeutisch Instituut Limburg   
Jacques Bernier, MD,  Study Chair,  Ospedale San Giovanni   
Jim Denham, MD,  Study Chair,  Newcastle Mater Misericordiae Hospital   
Volker Gustav Budach, MD, PhD,  Study Chair,  Universitaetsklinikum Charite   
Jean-Henri Bourhis, MD, PhD,  Study Chair,  Institut Gustave Roussy   
Ferenc Kaldau, MD,  Study Chair,  Radius Hungaricus Oncology Group   
Anna Sureda,  Study Chair,  Hospital de la Santa Cruz I Sant Pau   

Study ID Numbers:  CDR0000068669; EORTC-22996; ARO-EORTC-22996; EORTC-HN-22996; GORTEC-EORTC-22996; TROG-EORTC-22996; RHOG-EORTC-22996; GELCB-EORTC-22996
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017277
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08