Inclusion Criteria:

1. An informed consent form must be completed before any protocol specific screening. Patient must consent to a tissue biopsy at study entry and again at the week 3.
2. Patients must have a diagnosis of stage IIIb or stage IV non-small cell lung cancer (histologically or cytologically proven) and must not be eligible for combined chemotherapy and radiation therapy.
3. Patients must have at least one site of measurable disease that is amenable to biopsy. The patient must not have had radiation to this site. Lesion must be at least 20 mm in the longest diameter by spiral CT or 20 mm with conventional techniques according to RECIST.
4. Eligible patients must have an ECOG performance status of 0-1.

5. Patients must have adequate hepatic, renal, and bone marrow function as defined below: 1) Serum creatinine < 1.5 mg/dL or a calculated creatinine clearance > 60 mL/min 2)· Total bilirubin < 1.5 x ULN ·3) ALT or AST </= 2.5 x ULN OR ALT or AST </= 5.0 x ULN if related to liver metastases OR Alk Phos </= 2.5 x ULN ·4) WBC > 3,000/mm**3 ·5) ANC > 1,500 mm**3 ·6) Platelets > 100,000/mm**3 ·7) Hemoglobin > 10 g/dL

   • 8) PT/PTT < 1.5 x normal
6. Patients must be >= 18 years of age.

Exclusion Criteria:

1. Patients are excluded if they have received prior chemotherapy for this disease type.
2. Patients with brain metastases are not eligible for this study unless treated at least 4 weeks before entry and stable without steroid treatment for 1 week.
3. Prior radiation therapy allowed to <25% of the bone marrow. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment.
4. Patients may not have any concomitant uncontrolled medical or psychiatric disorders.
5. Patients must not be pregnant or breast-feeding. All women of childbearing potential must have a negative pregnancy test. Childbearing potential will be defined as women who have had menses within the past 12 months, who have not had tubal ligation or bilateral oophorectomy. There is no specific information available on the effects of this drug on women who are pregnant or breast-feeding. Therefore these patients are excluded from this study because of the unknown risks involved. All sexually active patients must practice adequate contraception for the entire treatment period.
6. Patients must not have undergone minor surgery (e.g., central venous catheter placement) within 24 hours of treatment with ZD6474. Patients may not have undergone any major surgery (e.g., laparotomy, thoracotomy, or craniotomy) within four weeks of enrollment.
7. Patients may not have a history of a bleeding diathesis.
8. Patients must agree not to use herbal remedies or other over-the-counter biologics (e.g., shark cartilage)
9. Significant cardiac event (including symptomatic heart failure or angina) within 3 months of entry or presence of cardiac disease that in the opinion of the Investigator increase the risk of ventricular arrythmia.
10. History of clinically significant arrhythmia (multifocal PVCs, bigeminy, trigeminy, ventricular tachycardia) which is symptomatic or requires treatment (CTC grade 3) or a symptomatic sustained ventricular tachycardia.
11. Chronic atrial fibrillation
12. Previous history of QT prolongation with other medication
13. Congenital long QT syndrome
14. QTc with Bazett's correction that is unmeasurable, or >/= 480 msec on screening ECG. If a patient has QTc >/= 480 msec on screening ECG, the screening may be repeated twice (at least 24 hours apart). The average QTc from the 3 screening ECGs must be < 480 msec in order for the patient to be eligible for the study.
15. Any concomitant medications that may cause QTc prolongation or induce Torsades de Points (see Appendix F) or induce CYP3A4 function (see section 8.2).
16. Potassium level less than 3.5 meq/l; calcium or magnesium level outside normal limits. Supplementation of electrolytes is permitted.
17. Left ventricular ejection fraction less than 45% measured by echocardiogram for subjects with previous anthracycline therapy (total dose greater than 450 mg/m2), significant cardiovascular disease, or chest irradiation
18. History of severe hypersensitivity reaction to drugs formulated with polysorbate 80
19. Use of drugs with known significant 3A4 inhibitory effects (i.e., ketoconazole, erythromycin, and verapamil) or drugs with known corneal toxicology (e.g., tamoxifen, chlorpromazine, amiodarone, and chloroquine). 5HT-3 antagonists may be used in this trial as anti-emetics.
20. Any concurrent condition which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
21. Participation in an investigational trial within the past 30 days.
22. Because of DCE-MRI, individuals with the following are excluded: 1) Cardiac pacemakers or neurostimulators, 2) Metal implants other than those approved as being safe in an MRI environment, 3) Claustrophobia, 4) Physical characteristics that preclude a MRI scan
23. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
24. Currently active diarrhea that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea.
25. Previous or current malignancies at other sites within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell carcinoma or squamous cell carcinoma of the skin