Phase II Study of Gamma Knife Radiosurgery and Temozolomide (Temodar) for Newly Diagnosed Brain Metastases

Inclusion Criteria:

- All subjects must have history of histologically confirmed malignancy. Brain biopsy
is not required unless diagnosis is judged to be in doubt by the treating physician.

- Newly diagnosed brain metastases (four or fewer by thin slice post-contrast MRI).

- ECOG performance status of less than or equal to 2 for patients with no prior
chemotherapy, and less than or equal to 1 for patients with prior chemotherapy.

- Age greater than 18

- Life expectancy greater than 12 weeks

- Subjects given written informed consent

- Adequate hematologic, renal and liver function as demonstrated by laboratory values
performed within 14 days, inclusive, prior to administration of study drug:

- Absolute neutrophil count (ANC) >= 1500/mm3

- Platelet count >= 100,000/mm3

- Hemoglobin >= 9 g/dL

- BUN and serum creatinine <= 1.5 times upper limit of laboratory normal

- Total and direct bilirubin <= 2 times upper limit of laboratory normal or in the
presence of documented liver metastases, total and direct bilirubin <=5 times
upper limit of normal

- SGOT and SGPT <= 2 times upper limit of laboratory normal or in the presence of
documented liver metastases, SGOT and SGPT <=5 times upper limit of normal

- Alkaline phosphatase <= 2 times upper limit of laboratory normal or in the
presence of documented liver metastases, alkaline phosphatase of <= 5 times
upper limit of normal

Exclusion Criteria:

- Patients with small cell lung cancer and lymphoma are ineligible.

- More than four metastases by thin slice MRI. Note that if a diagnostic study prior
to radiosurgery demonstrates only four tumors but the gamma knife treatment-planning
scan reveals greater than four tumors, the patients will still be eligible for the
protocol if all tumors can be treated with radiosurgery.

- Chemotherapy within four weeks prior to study drug administration

- Patients, who in the opinion of the treating medical oncologist, require immediate
cytotoxic chemotherapy other than the study drug. Allowed medications include
antihormonal agents (i.e., Tamoxifen), herceptin and bisphosphonates.

- Radiation therapy to greater than or equal to 50% of the bone marrow. Completion of
radiation therapy less than 4 weeks prior to study drug administration for
radiotherapy to >= 15% of bone marrow and less than 2 weeks prior for radiotherapy to
< 15% of bone marrow.

- Insufficient recovery from all active toxicities of prior therapies

- Subjects who are poor medical risks because of non-malignant systemic disease

- Frequent vomiting or medical condition that could interfere with oral medication
intake (e.g., partial bowel obstruction).

- Previous or concurrent malignancies at other sites, or treatment for malignancy at
the site within 5 years of study start with the exception of surgically cured
carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.

- Known HIV positively or AIDS-related illness.

- Pregnant or nursing women.

- Women of childbearing potential who are not using an effective method of
contraception. Women of childbearing potential must have a negative serum pregnancy
test 24 hours prior to administration of study drug and be practicing medically
approved contraceptive precautions.

- Men who are not advised to use an effective method of contraception.