Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer

OBJECTIVES:

Primary

• To compare the progression-free survival (PFS) of patients with locally advanced squamous cell carcinoma of the head and neck treated with standard fractionation radiotherapy and high-dose cisplatin vs accelerated fractionation radiotherapy and panitumumab.

Secondary

• To compare overall survival of patients treated with these regimens.
• To compare local and regional PFS of patients treated with these regimens.
• To compare distant metastasis in patients treated with these regimens.
• To compare adverse events, including late radiotherapy-related adverse events in patients treated with these regimens.
• To compare quality of life (QOL) of patients treated with these regimens.
• To compare swallowing-related QOL of patients treated with these regimens.
• To compare economic evaluation (cost effectiveness analysis and cost utility), including both healthcare utilization and indirect costs.

OUTLINE: This is a multicenter study. Patients are stratified according to T category (T1-3 vs T4), nodal status (N0-1 vs N2 vs N3), radiotherapy delivery modality (intensity-modulated [IMRT] vs 3-D conformal [3D CRT]), anatomic location (hypopharynx vs oral cavity vs oropharynx vs larynx), and participation in the optional swallowing impairment substudy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.
• Arm II: Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life (QOL) (FACT-H&N), swallowing-related QOL (MDADI, SWAL-QOL), swallowing function (FOIS), and economic evaluations (Lost Productivity questionnaire) are assessed periodically during the study.

After completion of study treatment, patients are followed periodically for at least 5 years.

DISEASE CHARACTERISTICS:

• Histologically and/or cytologically confirmed (primary lesion or regional lymph nodes) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx

• Locally advanced disease, defined by any of the following criteria:

• Any T, N+, M0
• T3-4, N0, M0
• No current history of unknown primary squamous cell carcinoma of the head and neck, primary nasopharyngeal, paranasal, or salivary gland tumors of the head and neck

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Absolute granulocyte count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 3 times ULN
• Creatinine clearance > 50 mL/min
• Magnesium > 0.5 mmol/L
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• Must be accessible for treatment and follow-up
• Able (sufficiently fluent) and willing to complete the quality of life (QOL) and swallowing QOL questionnaires in either English or French
• Must be assessed by a radiation oncologist and medical oncologist and deemed suitable for study participation
• No other malignancies within the past 5 years, except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other curatively treated solid tumors
• No history of allergic or hypersensitivity reactions to any of the study drugs or their excipients
• No prior or concurrent interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) on baseline CT scan
• No peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
• No hearing loss/tinnitus ≥ grade 3 (CTCAE v3.0)
• No thromboembolic event within the past 12 months despite being treated with anticoagulation drugs

• Prior thromboembolic event > 12 months allowed provided patient is stable on anticoagulation or on preventative anticoagulation
• None of the following allowed:

• Myocardial infarction within the past 12 months
• Uncontrolled severe congestive heart failure
• Unstable angina
• Active cardiomyopathy
• Unstable ventricular arrhythmia
• Uncontrolled hypertension
• Uncontrolled psychiatric disorder
• Active serious infection
• Active peptic ulcer disease
• Any other medical condition that might interfere with protocol therapy delivery

PRIOR CONCURRENT THERAPY:

• No prior surgical treatment except diagnostic biopsy for this disease
• No prior induction chemotherapy for this disease
• No prior radiation to the head and neck region that would result in overlap of fields for this study
• No prior cisplatin or carboplatin chemotherapy
• No prior targeted anti-EGFR therapy of any kind
• At least 30 days since any prior investigational agent
• No concurrent granulocytic growth factors (e.g., filgrastim [G-CSF]) during radiotherapy
• No concurrent erythropoietic growth factors, pilocarpine, amifostine, other anticancer therapy (e.g., cytotoxic agents, biological response modifiers, immunotherapy, or hormonal therapy), or other investigational drug therapy
• The following radiological investigations must be done within 8 weeks of randomization:

• MRI or CT of the head and neck
• CT chest