Inclusion Criteria:

- Histologically confirmed squamous cell carcinoma of the head and neck meeting one of
the following criteria:

- Recurrent disease

- Previously treated with standard curative therapy, including surgery and/or
radiotherapy with or without chemotherapy

- Newly diagnosed metastatic disease

- Must be deemed incurable by all of the following:

- Salvage surgery

- Radiotherapy

- Measurable disease ≥ 1 cm by conventional techniques, flexible fiberoptic
laryngoscopy, or examination under anesthesia

- No more than 2 prior conventional or investigational systemic therapies for
categorically incurable local-regional or distant disease

- No known primary brain tumor or brain metastases

- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- WBC > 3,000/mm³

- Absolute neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Hemoglobin > 8 g/dL

- Bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance > 60 mL/min

- Proteinuria ≤ +1 on 2 consecutive urine dipsticks taken ≥ 1 week apart

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- History of nonmelanoma skin cancer or other prior malignancy allowed provided the
cancer has been in remission for > 3 years

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to AZD2171

- No hypertension (i.e., systolic blood pressure (BP) > 160 mm Hg and diastolic BP >
100 mm Hg)

- No history of hypertensive urgency, hypertensive emergency, or end-organ damage
(i.e., thrombotic stroke, transient ischemic attacks, intracerebral hemorrhage,
myocardial infarction, aortic aneurysm, or aortic dissection)

- QTc ≤ 500 msec (with Bazett's correction)

- No history of familial long QT syndrome

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Bleeding diathesis

- Congestive heart failure, defined as New York Heart Association (NYHA) class
III-IV congestive heart failure

- NYHA class II congestive heart failure allowed provided there is increased
monitoring

- Significant ECG abnormality

- Peripheral vascular disease

- Unstable angina pectoris

- Cardiac arrhythmia

- Pulmonary edema

- Atrioventricular (AV) conduction abnormalities

- Sick sinus syndrome

- Second- or third-degree AV block

- Deep venous thrombosis

- No nonhealing ulcers, bone fracture, or wounds

- No psychiatric illness or social situation that would preclude study compliance

- No traumatic injury within the past 7 days

- No known coagulopathy that increases risk of bleeding

- No history of clinically significant hemorrhages

- See Disease Characteristics

- Recovered from all prior therapies

- No prior antiangiogenic therapy

- No more than 2 prior chemotherapy or antineoplastic regimens for categorically
incurable local-regional or distant disease

- At least 4 weeks since prior radiotherapy or major surgery

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

- More than 30 days since prior participation in an investigational trial

- No other concurrent investigational agents

- No concurrent drugs or biologics with proarrhythmic potential

- No concurrent anticoagulants (e.g., warfarin) or antiplatelet agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies