OBJECTIVES:

Primary

• Determine whether epoetin alfa given during definitive radiotherapy or chemoradiotherapy improves the local-regional control rate in anemic patients with squamous cell carcinoma of the head and neck.

Secondary

• Determine whether this drug improves survival in this patient population.
• Identify patterns in first failure in these patients.
• Determine whether there is a significant increase in hemoglobin level between the baseline value and the value at 28 days after starting epoetin alfa in these patients.
• Assess the toxicity of this regimen in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to stage (I/II vs III/IV without chemotherapy vs III/IV with chemotherapy), pretreatment hemoglobin level (9.0 to less than 11.5 g/dL vs 11.5 to 13.5 g/dL), and gender. Patients are randomized to one of two treatment arms.

• Arm I: Patients with stage I or II disease undergo radiotherapy once daily for 6-7 weeks. Patients with stage III or IV disease undergo radiotherapy once daily for 3.5 weeks and then twice daily (6 hours apart) for 2.5 weeks for a total of 6 weeks.
• Arm II: Patients undergo radiotherapy as in arm I. Beginning 7-10 days before radiotherapy, patients receive epoetin alfa subcutaneously once weekly until the end of radiotherapy.

Patients with stage III/IV disease may receive concurrent cisplatin IV over 1-2 hours on days 1 and 22 of radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 372 patients (186 per arm) will be accrued for this study within 3.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive squamous cell carcinoma of the head and neck, including carcinoma arising from the oral cavity, oropharynx, larynx, and hypopharynx

  • Stage I-IV disease
  • No distant metastases
  • No carcinoma of the nasopharynx, nasal cavity/paranasal sinuses, or salivary glands
  • No carcinoma in situ without an identifiable invasive component
• Plan for radiotherapy in continuous course
• Prior surgical exploration with gross residual disease remaining allowed
• Prior neck dissection with or without biopsy of primary tumor, but no radical surgery for primary tumor, allowed

• Anemia, defined as hemoglobin no greater than 13.5 g/dL for males and no greater than 12.5 g/dL for females (transfusion prior to study allowed)

  • No severe anemia (i.e., hemoglobin less than 9.0 g/dL)
  • No anemia confirmed to be due to causes other than chronic disease (e.g., iron deficiency anemia)
• Not entered on other RTOG head and neck protocols

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

• Stage III/IV patients receiving concurrent cisplatin:

  • Absolute neutrophil count at least 2,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

• Not specified

Renal:

• Stage III/IV patients receiving concurrent cisplatin:

  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance at least 50 mL/min

Cardiovascular:

• No malignant or poorly controlled hypertension (e.g., symptomatic hypertension or diastolic blood pressure of 100 mm Hg or greater despite antihypertensive medication)
• No unstable angina or other poorly controlled cardiac disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• If stage III or IV disease is present, willing to come for twice daily radiotherapy for the last 2.5 weeks of therapy
• No active infection requiring IV antibiotics
• No unexplained fever
• No AIDS or other history of congenital or acquired immunodeficiency
• No other malignancies within the past 3 years except carcinoma in situ or nonmelanomatous skin cancer
• No known hypersensitivity to mammalian cell-derived products or to human albumin
• No acute/subacute illness that would make the need for transfusion likely

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since other prior cytokine therapy (e.g., filgrastim [G-CSF], interleukins, or interferons)
• No prior epoetin alfa
• No other concurrent cytokine therapy

Chemotherapy:

• No prior chemotherapy
• Concurrent cisplatin, paclitaxel/cisplatin, or paclitaxel/carboplatin for patients with stage III/IV disease is allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to the head and neck

Surgery:

• See Disease Characteristics

Other:

• No concurrent amifostine
• No concurrent transfusion