Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma of the head and
neck, including any of the following subtypes:

- Oral cavity

- Oropharynx

- Larynx

- Hypopharynx

- Stage III or IV disease (no distant metastases)

- No cancer of the lip, nasopharynx, or sinuses

- Must have undergone gross total resection* (with curative intent) within 3-6 weeks of
registration, with pathology demonstrating 1 or more of the following risk factors:

- Histologic extracapsular nodal extension

- Invasive cancer seen on microscopic evaluation of the resection margin, when all
visible tumor has been removed NOTE: *Tonsillar cancer patients who undergo
transoral excision of all gross tumor are eligible if the patient has formal
neck dissection confirming histologic extracapsular nodal extension

PATIENT CHARACTERISTICS:

Inclusion criteria:

- Zubrod performance status 0-1

- ANC (absolute neutrophil count) ≥ 2,000/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve this level
allowed)

- Total bilirubin normal

- AST (aspartate aminotransferase) or ALT (alanine amino transferase) ≤ 2 times upper
limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN

- Serum creatinine ≤ 1.5 mg/dL

- Creatinine clearance ≥ 60 mL/min

- Glucose ≥ 40 mg/dL AND ≤ 250 mg/dL

- Sodium ≥ 130 mmol/L AND ≤ 155 mmol/L

- Magnesium ≥ 0.9 mg/dL AND ≤ 3 mg/dL (supplementation allowed)

- Potassium ≥ 4 mmol/L AND ≤ 6 mmol/L (supplementation allowed)

- Serum calcium (ionized or adjusted for albumin) ≥ 7 mg/dL AND ≤ 12.5 mg/dL
(supplementation allowed)

- QTc (corrected QT interval) interval ≥ 480 msec must have 2 additional EKGs ≥ 24 hrs
apart and the average QTc from the 3 screening EKGs must be < 480 msec

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 60 days
after completion of study treatment

- May not donate blood during the study or for 3 months after last dose of vandetanib

Exclusion criteria:

- Other simultaneous primary cancer

- Prior invasive malignancy (except nonmelanoma skin cancer) unless disease free for a
minimum of 3 years with the exception of the following:

- Carcinoma in situ of the cervix

- Adequately treated basal cell or squamous cell carcinoma of the skin

- Untreated or treated low-risk prostate cancer (defined as clinical or pathologic
T1c, N0 M0, PSA (prostate-specific antigen) < 10, Gleason < 7, < 50% of the
total cores positive for cancer)

- Severe, active co-morbidity, defined as follows:

- Clinically significant cardiovascular event (e.g., myocardial infarction,
superior vena cava syndrome, or New York Heart Association class II-IV) or
presence of cardiac disease that, in the opinion of the investigator, increases
the risk of ventricular arrhythmia within the past 3 months

- Unstable angina and/or congestive heart failure requiring hospitalization within
the past 3 months

- Transmural myocardial infarction within the past 3 months

- History of arrhythmia (e.g., multifocal premature ventricular contractions,
bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial
fibrillation) which is symptomatic or requires treatment (CTCAE [Common
Terminology Criteria for Adverse Events] grade 3), or asymptomatic sustained
ventricular tachycardia

- Patients with atrial fibrillation, controlled on medication, are eligible

- Presence of left bundle branch block

- Previous history of QTc prolongation as a result from other medication that
required discontinuation of that medication

- Congenital long QTc syndrome or first degree relative with unexplained sudden
death under 40 years of age

- QTc with Bazett's correction that is unmeasurable or ≥ 480 msec on screening EKG

- Patients who are receiving a drug that has a risk of QTc prolongation are
not eligible if QTc is ≥ 460 msec

- Hypertension (systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm
Hg) not controlled by medical therapy

- Diarrhea ≥ grade 1 (increase of < 4 stools per day over baseline or mild
increase in ostomy output compared to baseline)

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

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

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

- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC (Center for
Disease Control) definition (no HIV testing is required for study entry)

- Prior allergic reaction to cisplatin or vandetanib or derivatives similar to these
drugs

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior systemic chemotherapy for this disease (prior chemotherapy for a different
cancer allowed)

- No prior radiotherapy to the head and neck area that would result in overlap of
radiotherapy fields

- More than 30 days since prior investigational agents

- More than 3 weeks since prior major surgery and recovered

- More than 2 weeks since prior and no concurrent medications that induce Torsades de
Pointes

- More than 2 weeks since prior and no concurrent known potent inducers of CYP3A4
(Cytochrome P450 3A4), including rifampicin, phenytoin, carbamazepine, barbiturates,
and Hypericum perforatum (St. John wort)

- No concurrent medication that may cause QTc prolongation