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

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