Inclusion Criteria:

1. The patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or
fine-needle aspiration.

2. The patient has a diagnosis of either stage IIIB, stage IV, or advanced, incurable
NSCLC, and failed at least one front-line metastatic NSCLC chemotherapy regimen.
(Patients who have failed adjuvant or locally advanced therapy within 6 months are
also eligible to participate in study).

3. The patient has uni-dimensionally measurable NSCLC.

4. Karnofsky performance status >/= 60 or Eastern Cooperative Oncology Group (ECOG)
performance status 0-2

5. The patient has biopsy accessible tumor.

6. The patient has adequate hematologic function as defined by an absolute neutrophil
count (ANC) >/= 1,500/mm^3, platelet count >/= 100,000/mm^3, White Blood Count (WBC)
>/= 3,000/ mm^3, and hemoglobin >/= 9 g/dL.

7. The patient has adequate hepatic function as defined by a total bilirubin level 1.5 times the upper limit of normal, and alkaline phosphatase, Alanine
aminotranferease (ALT) or aspartate aminotransferase (AST) limit of normal.

8. The patient has adequate renal function as defined by a serum creatinine level 1.5 mg/dL or a calculated creatinine clearance of >/= 60cc/minute.

9. The patient has prothrombin time (PT) < 1.5 times upper limit of normal

10. If patient has brain metastasis, they must have been stable (treated or asymptomatic)
for at least 4 weeks after radiation if treated with radiation and not have used
steroids for at least 1 week. Re-imaging performed after 2 weeks, upon completion of
radiation therapy.

11. The patient is >/= 18 years of age.

12. The patient has signed informed consent.

13. The patient is eligible if disease free from a previously treated malignancy, other
than a previous NSCLC, for greater than two years. Patients with a history of prior
basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are exempt
from exclusion.

14. Women of childbearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation.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.Should a woman become pregnant or suspect that she is pregnant
while participating in this study,she should inform her treating physician
immediately.The patient,if a man,agrees to use effective contraception or abstinence.

15. Subject must be considered legally capable of providing his or her own consent for
participation in this study.

Exclusion Criteria:

1. The patient has received prior investigational therapy, chemotherapy, surgery, or
radiotherapy within 4 weeks of initiating study drug

2. The patient has undergone prior thoracic or abdominal surgery within 28 days of study
entry, excluding prior diagnostic biopsy.

3. The patient has received radiation therapy to the measurable tumor within 6 months.
Patients are allowed to have local irradiation for the management of tumor-related
symptoms (bones, brain). However, if a patient has active new disease growing in the
previously irradiated site, the patient will be eligible to participate in the study.

4. The patient has a significant medical history or unstable medical condition (unstable
systemic disease: congestive heart failure (New York Heart Association Functional
Classification class II or worse), recent myocardial infarction within 3 months,
unstable angina, active infection (i.e. currently treated with antibiotics),
uncontrolled hypertension). Patients with controlled diabetes will be allowed.
Patient must be able to undergo procedure for tissue acquisition.

5. The patient has uncontrolled seizure disorder, active neurologic disease, or
neuropathy >/= grade 2. Patients with meningeal or CNS involvement by tumor are
eligible for the study if the above exclusion criteria are not met.

6. The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.

7. Any condition that is unstable or could jeopardize the safety of the patient and its
compliance in the study, in the investigator's judgment

8. The patient is actively taking herbal remedies or over-the-counter biologics (e.g.,
shark cartilage, high dose antioxidants).

9. Patients will be allowed to have prior biologic (i.e. VEGF, EGFR, etc.) therapy.
However, the patient will be excluded from a given study if he/she has received the
same therapy as the clinical trial (i.e. If a patient has been previously treated
with bevacizumab, they are allowed to enroll in any of the 4 studies. If a patient
has been previously treated with erlotinib, they are excluded from the clinical
trials with erlotinib). In addition, if a patient has been previously treated with
gefitinib (Iressa), they are excluded from the clinical trials with erlotinib.

10. 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.

11. Patients may not have a history of a bleeding diathesis.

12. Significant cardiovascular event (e.g. myocardial infarction, superior vena cava
syndrome (SVC), New York Heart Association (NYHA) classification of heart disease
>/=2 within 3 months of entry of presence of cardiac disease that in the opinion of
the investigator increases the risk of ventricular arrhythmia

13. 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. Atrial fibrillation, controlled on
medication is not excluded.

14. Prior history of QT prolongation as a result from other medication that required
discontinuation of that medication.

15. Congenital long QT syndrome or 1st degree relative with unexplained sudden death
under 40 years of age.

16. 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 screen ECG may be repeated
twice (at least 24 hours apart). The average QTc from the three screening ECGs must
be <480 msec in order for the patient to be eligible for the study). If the patient
meets eligibility requirements in this way, the "baseline" QTc for this patient will
be the average of the 3 ECGs (screen 1, screen 2, and pre-1st dose). Patients who are
receiving a drug that has a risk of QTc prolongation are excluded if QTc is >/= 460
msec.

17. Any concomitant medications that affect QTc, induce Torsades de Pointes. (lists of
relevant medications available that have a risk of Torsades de Pointes or QTc
prolongation.) Drugs listed that in the investigator's opinion cannot be
discontinued, are allowed however, must be monitored closely.

18. Potassium, calcium (ionized calcium or adjusted for albumin), or magnesium
concentrations outside normal limits. Supplementation of electrolytes is permitted.
Potassium level must be greater than or equal to 4.0 meq/L.

19. Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin,
carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function.

20. Hypertension not controlled by medical therapy (systolic blood pressure greater than
160 mm Hg or diastolic blood pressure greater than 100 mm Hg)

21. Presence of left bundle branch block (LBBB.)

22. Any unresolved toxicity greater than common terminology criteria (CTC) grade 1 from
previous anti-cancer therapy.

23. Currently active diarrhea that may affect the ability of the patient to absorb the
ZD6474 or tolerate diarrhea.