Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

Inclusion Criteria:

• Histologically confirmed cancer of the nasopharynx based on biopsy of a primary lesion and/or lymph nodes

• Histologic WHO types I-IIb/III

• Stage IIB-IVB disease

• No T1-2, N1 disease in which node positivity is based on the presence of retropharyngeal lymph nodes

• No distant metastases

• Zubrod performance status 0-1

• WBC ? 4,000/mm?

• Hemoglobin ? 9.0 g/dL

• Platelet count ? 100,000/mm?

• Absolute neutrophil count ? 1,500/mm?

• INR ? 1.5

• aPTT ? 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase ? 1.5 times ULN

• ALT and AST ? 1.5 times ULN

• Bilirubin ? 1.5 times ULN

• Creatinine ? 1.5 mg/dL OR creatinine clearance ? 55 mL/min

• Urine protein:creatinine (UPC) ratio < 1.0

• If UPC > 0.5, 24-hour urine protein must be < 1,000 mg

• Hearing loss primarily sensorineural in nature and requiring a hearing aid or intervention that interferes in a clinically significant way with activities of daily living allowed

• Conductive hearing loss from tumor-related otitis media is allowed

• No severe, active comorbidity, including any of the following:

• Ongoing bleeding diathesis, hemorrhagic disorder, or coagulopathy within the past 6 months

• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

• Esophageal varices, nonhealing wound, nonhealing ulcer, or bone fracture within the past 6 months

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days

• Unstable angina and/or congestive heart failure or peripheral vascular disease requiring hospitalization within the past 12 months

• Major medical or psychiatric illness that, in the opinion of the study investigator, would preclude study compliance

• Active, untreated infection and/or acute bacterial or fungal infection requiring intravenous antibiotics

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

• History of significant weight loss (> 15% from baseline)

• History of arterial thromboembolic events

• Acquired immune deficiency syndrome

• Transmural myocardial infarction

• Cerebrovascular accident

• Transient ischemic attack

• Any other cardiac condition that, in the opinion of the investigator, would preclude study compliance

• No gross hemoptysis or hematemesis, defined as bright red blood of ? 1 teaspoon per coughing episode, within the last 4 weeks (incidental blood mixed with phlegm allowed)

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

• Nutritional and physical condition considered suitable for study treatment

• No significant traumatic injury within the past 4 weeks

• No history of allergic reaction to the study drugs

• No baseline blood pressure > 150/100 mm Hg

• No peripheral neuropathy ? grade 2

• Not pregnant or nursing

• Negative serum pregnancy test

• Fertile patients must use effective contraception during and for ? 6 months after completion of study treatment

• At least 10 days since prior and no concurrent dipyridamole, ticlopidine, clopidogrel bisulfate, cilostazol, warfarin, heparin, daily treatment with acetylsalicylic acid (> 325 mg/day), or nonsteroidal anti-inflammatory medications known to inhibit platelet function

• No prior head and neck surgery of the primary tumor or lymph nodes except for incisional or excisional biopsies

• More than 15 days since prior biopsies

• More than 1 week since prior fine-needle aspirations or placement of percutaneous gastrostomy tube

• More than 4 weeks since prior major surgical procedures

• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• No prior bevacizumab or other vascular endothelial growth factor-targeting agents

• No prior systemic chemotherapy for the study cancer

• Prior chemotherapy for a different cancer allowed

• No concurrent hematologic growth factors (e.g. filgrastim [G-CSF], darbepoetin alfa, epoetin alfa) during study chemoradiotherapy

• No concurrent prophylactic growth factors for neutropenia during study adjuvant therapy

• No concurrent prophylactic amifostine or pilocarpine

• No other concurrent experimental therapeutic cancer treatments