Radiation Therapy With or Without Epoetin Alfa in Treating Patients With Head and Neck Cancer

A Phase III Double-Blind, Randomized, Placebo-Controlled Study of Erythropoietin When Used as an Adjuvant to Radiation Therapy in Patients With Head and Neck Squamous Cell Carcinoma

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.

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.

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