Inclusion Criteria:

• Histological or cytological proof of chemotherapy-naïve, extensive, small cell lung cancer.
• Measurable disease according to RECIST and obtained by imaging within 28 days prior to being registered for protocol therapy.
• Written informed consent and HIPAA authorization for release of personal health information.
• Age 18 years or older at the time of consent.
• Potassium ≥4.0 mmol/L and <5.5mmol/L (supplementation is allowed).
• Calcium within normal range (supplementation is allowed).
• Magnesium within normal range (supplementation is allowed).

Exclusion Criteria:

• No prior EGFR inhibitor or antiangiogenic agent allowed.
• No prior hormonal therapy.
• No symptomatic brain metastasis.
• No clinically significant infections as judged by the treating investigator.
• No evidence of severe or uncontrolled other systemic disease or 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.
• No previous history of QTc prolongation as a result of medication that required discontinuation of that medication.
• No congenital long QT syndrome or known 1st degree relative with unexplained sudden death under 40 years of age.
• No presence of left bundle branch block (LBBB.)
• No QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG obtained within 7 days prior to registration for protocol therapy. If a subject 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 subject to be eligible for the study.
• No concomitant (within 14 days prior to registration for and during protocol therapy) medication associated with Torsades de Pointes or cause QTc prolongation, is allowed. Medications that prolong QT, but are not strictly associated with Torsades, are allowed if medically necessary and will require increased ECG and electrolyte monitoring.
• No uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg).
• No currently active diarrhea that may affect the ability to absorb ZD6474.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the subject has been disease-free for at least 5 years.
• Major surgery must be completed greater than 28 days prior to registration for protocol therapy and healed surgical incision is required.
• No concomitant (within 14 days prior to registration for and during protocol therapy) medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function.
• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
• Females must not be breastfeeding.