The purpose of this study is to determine whether treatment with temozolomide will shrink small cell lung cancer tumors. Temozolomide is an oral chemotherapy drug that is currently used to treat brain cancer and melanoma.

As part of this study, we will be doing additional tests that may help us understand how temozolomide works. First, if there is a tumor sample from a biopsy done in the past, it will be analyzed for an abnormal gene that may be present in lung cancer. Before starting temozolomide, a research blood test will be done to look for the same abnormal gene we are looking for in your tumor sample. Also, before starting temozolomide and every time you have a repeat CT scan, a research blood test will be done to analyze the number of tumor cells in your bloodstream.

Inclusion Criteria:

• Patients must have pathologically confirmed SCLC at MSKCC that has progressed after one or two chemotherapy regimens.
• At least 3 weeks must have elapsed since last chemotherapy or radiation treatment and initiation of study treatment.
• Karnofsky performance status > or = to 60%.
• Patients must have measurable disease, this can include brain metastases.
• Patients must have normal organ and marrow function as defined below:
• - leukocytes > 3,000/mcL
• platelets > 100,000/mcL
• total bilirubin < 1.5 mg/dL
• AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal
• Creatinine < 2.0 mg/dl
• For women of child-bearing potential, negative pregnancy test within 7 days prior to starting temozolomide.
• Men and women of childbearing potential must agree to practice adequate contraception.
• 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 not recovered from adverse events of previous therapies.
• Patients receiving other investigational agents.
• Patients with leptomeningeal involvement.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition or HIV-positive patients on combination antiretroviral therapy. However, HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because these patients are at increased risk of lethal infections when treated with marrow- suppressive therapy. Excluding patients on HAART is necessary due to the potential for pharmacokinetic interactions with temozolomide.
• Women who are pregnant or breast feeding, due to possible adverse effects on the developing fetus or infant due to study drug.