Randomized Phase II Study: Temozolomide (TMZ) Concomitant to Radiotherapy Followed by Sequential TMZ in Advanced NSCLC Patients With CNS Metastasis Versus Radiotherapy Alone

Inclusion Criteria:

- Prior histologic confirmation of non-small cell lung cancer (NSCLC).

- Optional: NSCLC histologic confirmation of metastasis of NSCLC.

- Presence of unidimensionally measurable disease in the brain.

- No previous or current malignancies at other sites with the exception of adequately
treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin.

- Age: >18 years.

- Subjects must not have systemic disease that in the opinion of the investigator is in
immediate need of chemotherapy

- Karnofsky Performance status >=70%.

- Absolute neutrophil count (ANC) >1,500/mm^3, platelets >100,000/mm^3, hemoglobin >8
g/dL.

- Serum creatinine and bilirubin <1.5 times upper normal limit of testing laboratory.

- Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase
(SGPT) <3 times upper limit of testing laboratory.

- Palliative radiation therapy to thorax and bone or other organs (except brain) is
acceptable.

- Prior neurosurgery >2 weeks from initiating treatment with temozolomide.

- Cortisone medication stable or decreasing within 2 weeks prior to initiating
treatment with temozolomide.

- Patient is not pregnant or nursing and is advised and willing to use an effective
method of contraception.

- Written informed consent.

Exclusion Criteria:

- Chemotherapy or biologic therapy within four weeks prior to initiating therapy with
temozolomide.

- Prior radiation therapy for brain <4 weeks from initiating therapy with temozolomide.

- Surgery within two weeks prior to temozolomide administration.

- RPA class III

- Patients with a single brain metastasis amenable to radiosurgery of resection

- Known HIV disease.

- Acute infection requiring intravenous antibiotics.

- Any reason making compliance to the protocol improbable.