A Phase III Trial for Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy Versus Chemotherapy Alone

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically* or cytologically* confirmed squamous cell carcinoma (SCC) of the oral
cavity, oropharynx, hypopharynx, or larynx, including any of the following histologic
variants:

- Spindle cell carcinoma

- Poorly differentiated keratin-positive carcinoma

- Lymphoepithelioma NOTE: *Biopsy or primary tumor and/or fine needle aspiration
of the metastatic lymph node required

- Original or second primary tumor

- Recurrent neck metastases with unknown primary allowed

- Locally recurrent disease

- Measurable disease

- Unresectable disease

- Attempted surgical resection allowed provided surgery was performed ≥ 3 months
ago, wound is completely healed, and there is no sign of carotid exposure

- Must have had prior radiotherapy for SCC of the head and neck with > 75% of the
present tumor volume in areas irradiated at doses ≥ 45 Gy but ≤ 75 Gy

- Able to successfully re-irradiate the area of the gross tumor volume without
exceeding lifetime spinal cord dose of 54 Gy as determined by physical
examination and CT scan and/or MRI performed within the past 8 weeks

- First recurrence occurred > 6 months after completion of radiotherapy

- More than 1 recurrence allowed provided the above criteria for first
recurrence has been met

- No primary tumor of the nasopharynx or salivary gland

- No distant metastases by history or physical examination, chest CT scan, and CT scan
or MRI of the tumor site

- Patients with equivocal pulmonary nodules are eligible provided the nodules are
< 1 cm, can be safely biopsied, or are negative by positron emission tomography
imaging

- No circumferential tumor involvement of the carotid sheath by imaging unless
prophylactic carotid stent is placed

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-1

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,800/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)

Hepatic

- AST or ALT < 2 times upper limit of normal (ULN)

- Bilirubin < 1.5 mg/dL

- No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

Renal

- Creatinine clearance > 50 mL/min

- Calcium < 11.5 mg/dL

Cardiovascular

- No New York Heart Association class III or IV heart disease

- No other symptomatic or uncontrolled cardiac disease

Pulmonary

- No chronic obstructive pulmonary disease exacerbation

- No other respiratory illness requiring hospitalization within the past 6 months or
that would preclude study therapy

Immunologic

- No AIDS

- No prior allergic reaction to E. coli-derived products

- No acute bacterial or fungal infection requiring IV antibiotics

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 30 days after
completion of study treatment

- No other invasive malignancy within the past 3 years except nonmelanoma skin cancer,
carcinoma in situ of the breast, oral cavity, or cervix

- No pre-existing peripheral sensory neuropathy > grade 2

- No other severe active co-morbidity

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- At least 6 months since prior chemotherapy

- No prior systemic chemotherapy for recurrent SCC of the head and neck

- Prior neoadjuvant, adjuvant, and/or concurrent chemotherapy and radiotherapy for
initial SCC of the head and neck allowed

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

- See Chemotherapy

- At least 6 months since prior radiotherapy

Surgery

- See Disease Characteristics

Other

- Prior cyclooxygenase-2 inhibitor or retinoids for chemoprevention allowed

- At least 6 months since prior epidermal growth factor receptor (EGFR) inhibitors or
other targeted agents

- No prior EGFR inhibitors or other targeted agents for recurrent SCC of the head and
neck

- No concurrent cimetidine or allopurinol (for patients on arm II, regimen 1)