Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with CT scan.
• Patients must be chemotherapy naive.
• Previous radiotherapy is allowed only if < 30% of marrow bearing bones were irradiated and if radiotherapy was completed at least 2 weeks prior to enrollment and the patient has recovered from all adverse effects of prior radiotherapy.
• Age >18 years.
• Life expectancy of greater than 3 months.
• ECOG performance status <2 (Karnofsky >60%).
• Adequate organ and marrow function.
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or double barrier method of birth control) prior to study entry and for the duration of study participation.
• Ability to understand and the willingness to sign a written informed consent document.
• Both men and women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

• Patients who have had chemotherapy or any other investigational agent for any indication within 30 days of study enrollment.
• Patients who have had radiotherapy within 2 weeks, prior to entering the study or those who have not recovered from adverse events due to these therapies.
• Patients with known brain metastases are excluded.
• Patients who have been previously treated with an HDAC inhibitor (use of valproic acid is allowed with a 30-day washout).
• Patients with peripheral neuropathy CTC grade >2 are excluded.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any major surgery within 2 weeks prior to enrollment. Minimally invasive procedures for the purpose of diagnosis or staging of the disease are permitted.
• History of another malignancy in the last 5 years. Patients with prior history of in situ cancer, basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone and have been continuously disease free for at least 5 years.
• Pregnant women are excluded from this study because irinotecan and paclitaxel are antineoplastic agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with agents used in this trial, breastfeeding should be discontinued if the mother is treated with these agents.
• Patients with known HIV, Hepatitis B, Hepatitis C or active Hepatitis A are excluded.
• Patients on any systemic steroids for any indication, with doses that have not been stabilized to the equivalent of < 10 mg/day prednisone during the 30 days prior to study enrollment. This does not include short courses of steroids administered at high doses.
• Patients with the inability to absorb oral vorinostat.
• Patients with known allergy or hypersensitivity to any component of any of the study therapies.