RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Paclitaxel albumin-stabilized nanoparticle formulation may make tumor cells more sensitive to radiation therapy. Giving radiation therapy and paclitaxel albumin-stabilized nanoparticle formulation together with cisplatin and cetuximab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with cisplatin, cetuximab, and radiation therapy to see how well they work in treating patients with locally advanced stage III or stage IV head and neck cancer.

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of paclitaxel albumin-stabilized nanoparticle formulation when combined with cisplatin, cetuximab, and radiotherapy in patients with local-regionally advanced squamous cell carcinoma of the head and neck. (Phase I)
• To evaluate the disease-free survival of patients treated with this regimen. (Phase II)

Secondary

• To identify dose-limiting toxicities in these patients treated with this regimen. (Phase I)
• To assess the safety and tolerability of this regimen. (Phases I and II)
• To assess progression-free survival and survival of patients treated with this regimen. (Phase I)
• To assess overall survival in patients treated with this regimen. (Phase II)
• To assess response rates in patients treated with this regimen. (Phases I and II)

OUTLINE: This is a multicenter, phase I dose-escalation study of paclitaxel albumin-stabilized nanoparticle formulation followed by a phase II study.

Patients receive cetuximab IV over 120 minutes in week 1. Patients then receive cetuximab IV over 60 minutes, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, and cisplatin IV over 60 minutes once weekly in weeks 2-8. Patients also undergo 3D conformal or intensity-modulated radiotherapy over 30 minutes on days 1-5 in weeks 2-8.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, or larynx

  • Diagnosis based on the primary lesion and/or lymph nodes
  • Stage III or IV disease (T2, N2-3, M0 or T3-4, any N, M0)

• No primary tumor of the oral cavity, nasopharynx, sinuses, or salivary glands

• No distant metastasis by chest x-ray, CT scan, or PET/CT scan within the past 6 weeks

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• ANC > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Hemoglobin > 9.0 g/dL (transfusion or other intervention to achieve hemoglobin > 8.0 g/dL allowed)

• Bilirubin ≤ 1.5 mg/dL

• AST, ALT, and AP ≤ 2.5 times upper limit of normal

• Serum creatinine ≤ 1.5 mg/dL

• Creatinine clearance ≥ 50 mL/min

• None of the following electrolyte abnormalities grade 3-4 by CTCAE v 3.0:

  • Calcium < 7 mg/dL or > 12.5 mg/dL
  • Glucose < 40 mg/dL or > 250 mg/dL
  • Magnesium < 0.9 mg/dL or > 3 mg/dL
  • Potassium < 3 mmol/L or > 6 mmol/L
  • Sodium < 130 mmol/L or > 155 mmol/L

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other prior invasive malignancy, except for nonmelanomatous skin cancer, unless disease-free for ≥ 3 years

• No prior allergic reaction to study drugs

• No active cardiac disease, defined as any of the following:

  • Unstable angina
  • Uncontrolled hypertension
  • Myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass graft or percutaneous transluminal coronary angioplasty)
  • Uncontrolled arrhythmia
  • Congestive heart failure
  • Three or more heart-related hospitalizations within the past year

• No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year

• No AIDS

• No pre-existing peripheral sensory neuropathy ≥ grade 2

• No concurrent medical illnesses that would impair patient tolerance to therapy or limit survival

PRIOR CONCURRENT THERAPY:

• No prior systemic chemotherapy for this cancer

  • Prior systemic chemotherapy for a different cancer allowed

• No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields

• No prior initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease)

• At least 48 hours since prior and no concurrent granulocytic growth factors (e.g., filgrastim [G-CSF]) during radiotherapy

• No concurrent erythropoietic growth factors (e.g., darbepoetin, erythropoietin)