Treatment of Malignant Pleural Effusion With ZD6474, a Novel Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor

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)
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 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