Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed locally advanced or metastatic (stage IIIB pleural effusion
or stage IV) non-small cell lung cancer (NSCLC), including the following cell types:

- Squamous cell carcinoma

- Adenocarcinoma

- Adenosquamous carcinoma

- Large cell carcinoma

- Large cell neuroendocrine

- Carcinoma not otherwise specified

- Measurable disease as defined by RECIST

- Clinically stable brain metastases are permitted

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Serum potassium ≥ 3.8 mmol/L and magnesium ≥ 2.0 mg/dL

- Electrolyte abnormalities may be corrected with supplementation

- Hemoglobin ≥ 10 g/dL (transfusions and/or erythropoietin-stimulating agents are
permitted)

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT < 2.0 times ULN (< 3 times ULN in the presence of demonstrable liver
metastases)

- Serum creatinine < 2.0 times ULN

- Not pregnant or nursing

- Negative urine or serum pregnancy test

- Women of childbearing potential and men must use an effective barrier method of
contraception (e.g., an intrauterine contraception device [IUCD], double-barrier
method using condoms, or a diaphragm plus spermicide) during the treatment period and
for at least 1 month thereafter

- No known cardiac abnormalities, including any of the following:

- Congenital long QT syndrome

- QTc interval > 480 msec

- Myocardial infarction within 12 months prior to study entry

- Other significant electrocardiogram (ECG) abnormalities, including type II
second- or third-degree atrio-ventricular (AV) block, or bradycardia
(ventricular rate < 50 beats/min)

- History of coronary artery disease (CAD) (e.g., angina Canadian class II-IV)

- For any patients in whom there is doubt, a stress-imaging study should be
performed and if abnormal, an angiography should also be performed to
define whether or not CAD is present

- An ECG recorded at screening showing significant ST depression (ST depression of
≥ 2 mm, measured from isoelectric line to the ST segment at a point 60 msec from
the end of the QRS complex)

- NYHA class II to IV congestive heart failure (CHF), and/or ejection fraction
(EF) < 40% by MUGA scan or < 50% by ECG and/or MRI

- Known history of sustained ventricular tachycardia (VT), ventricular
fibrillation (VF), Torsades de Pointes, or cardiac arrest, unless currently
addressed with an automatic implantable cardiac defibrillator (AICD)

- Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment
or other causes

- Uncontrolled hypertension defined as blood pressure ≥ 160/95 mm Hg

- Any cardiac arrhythmia requiring anti-arrhythmia medication

- No clinically significant active systemic, pulmonary, or pericardial infection,
including known HIV infection and hepatitis B or C

- No significant medical or psychiatric condition that might prevent the patient from
complying with all study procedures

PRIOR CONCURRENT THERAPY:

- At least 3 weeks since prior erlotinib hydrochloride (phase I)

- At least 3 weeks since prior anti-cancer therapy or, at the discretion of the
investigator, may be treatment-naive (phase I)

- At least 1 and no more than 2 prior chemotherapy regimens for advanced NSCLC (phase
II)

- At least 3 weeks since prior chemotherapy for NSCLC

- At least 2 weeks since prior major surgery or radiation therapy

- No prior erlotinib hydrochloride (phase II)

- No prior romidepsin

- No other concurrent anti-cancer therapy

- No prior or concurrent investigational agent within 4 weeks prior to study entry

- No concurrent drugs that may cause a prolongation of the QTc interval

- No concurrent CYP3A4 inhibitors

- No concurrent warfarin