OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of bevacizumab when given in combination with fluorouracil, hydroxyurea, and radiotherapy in patients with advanced head and neck cancer.
• Determine the time to progression, pattern of failure, local control, and distant failure rate in patients treated with this regimen.
• Determine the local toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of bevacizumab.

Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive filgrastim (G-CSF) subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 27-39 patients will be accrued for this study within 5.4-19.5 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced head and neck cancer

  • Requiring regional palliative radiotherapy
  • Not amenable to standard therapy
• Previously untreated disease allowed only if prognosis is poor (i.e., estimated 2-year survival of less than 10% if treated with standard therapy alone)
• No obvious tumor involvement of major vessels on CT scan
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• More than 12 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No history of bleeding diathesis

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal
• Urine protein no greater than trace OR
• Urine protein less than 0.5 g/24 hours
• No significant renal impairment

Cardiovascular:

• No symptomatic congestive heart failure
• No cardiac arrhythmia
• No deep venous thrombosis
• No uncontrolled hypertension
• No clinically significant peripheral artery disease

• No arterial thromboembolic event within the past 6 months, including any of the following:

  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina
  • Myocardial infarction

Pulmonary:

• No hemoptysis of at least 1 tablespoon

Other:

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in this study
• No non-healing wounds within the past 4 weeks
• No significant ongoing or active infection
• No other uncontrolled illness
• No other severe complicating medical illness that would preclude study participation
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior fluorouracil and hydroxyurea with radiotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• See Chemotherapy
• At least 4 months since prior radiotherapy and recovered

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No prior or concurrent chronic use of aspirin or other nonsteroidal anti-inflammatory agents
• No other concurrent investigational agents
• No concurrent anticoagulation therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents