Inclusion Criteria:

1. Patients with pleural effusion requiring placement of an indwelling intrapleural denver catheter for recurrent symptomatic malignant pleural effusion
2. Pathologic documentation of NSCLC
3. Performance status 0 to 2 (Eastern Cooperative Oncology Group (ECOG) scale)
4. International Normalized Ratio (INR) </= 2.5
5. Signed informed consent prior to any study related procedures
6. Subject must be female or male age 18 years or over

Exclusion Criteria:

1. Chemotherapy or other anticancer therapy in the 3 weeks prior to study. Palliative radiotherapy will be allowed to extra thoracic sites 2 weeks prior to study
2. No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for at least two years
3. Laboratory results sustained at:Neutrophils less than 1.5x10^9/L or platelets less than 100x10^9/L; Serum bilirubin >1.5 x the upper limit of reference range (ULRR);Serum creatinine>1.5xULRR or CrCl </=30 mL/minute(calculated by Cockcroft-Gault formula). Potassium,<4.0 mmol despite supplementation;serum calcium (ionized or adjusted for albumin),or magnesium out of normal range despite supplementation;Alanine aminotransferase(ALT)or aspartate aminotransferase(AST) > 2.5 x ULRR or alkaline phosphatase(ALP)> 2.5 x ULRR,or > 5 x ULRR if judged by the investigator to be related to liver metastases
4. Serious underlying medical condition that would impair the ability of the patient to receive protocol treatment, specifically cardiac diseases, uncontrolled hypertension or renal diseases
5. Diagnosis of post-obstructive pneumonia or other serious infection in the 14 days prior to registration
6. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
7. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
8. Clinically significant cardiovascular event such as Myocardial infarction; New York Heart Association (NYHA) classification of heart disease >/=2 within 3 months before entry; or presence of cardiac disease that in the opinion of the Investigator increase the risk of ventricular arrhythmia
9. History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded
10. Previous history of QTc prolongation with other medication that required discontinuation of that medication
11. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
12. 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). Patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is >/= 460 msec
13. Any concomitant medication that may cause QTc prolongation or induce Torsades de Pointes
14. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
15. Women who are currently pregnant or breast feeding
16. Participation in a clinical trial of any investigational agents within 30 days prior to commencing study treatment
17. In 2nd line or later, the last dose of prior chemotherapy is discontinued less than 3 weeks before the start of study therapy
18. In 2nd line or later, the last radiation therapy discontinued less than 2 weeks before the start of study therapy except palliative radiotherapy
19. If it is in 2nd line or later, any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy
20. Previous enrollment or randomization of treatment in the present study
21. Patients with pre-existing placement of intrapleural catheter
22. Presence of left bundle branch block (LBBB.)
23. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
24. Patients may not have a history of a bleeding diathesis
25. Currently active diarrhea that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea
26. Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function