Temozolomide in Treating Patients With Solid Tumors That Have Spread to the Brain

Inclusion Criteria

• •Age greater than or equal to 18 years.
• •Karnofsky performance status (KPS) of greater than or equal to 60.
• •Laboratory values (performed within 14 days prior to study drug administration, inclusive).
• •Absolute neutrophil count (ANC) \>1500/mm3
• •Platelet count \>100,000/mm3
• •Hemoglobin \>10 g/dl or 100 g/l
• •BUN and serum creatinine \<1.5 times upper limit of laboratory normal
• •Total and direct bilirubin \<1.5 times upper limit of laboratory normal
• •SGOT and SGPT \< 3 times upper limit of laboratory normal
• •Alkaline Phosphatase \< 3 times upper limit of laboratory normal
• •A life expectancy from disease outside the CNS of greater than 12 weeks.
• •Subjects must give written informed consent.
• •Subjects must have histologically confirmed advanced solid malignancy with brain metastases, with or without systemic disease.
• •Subjects must have failed or refused prior standard therapy for cerebral metastases and have imaging evidence of progressive disease. Prior therapy may include surgery and/or whole brain radiotherapy and/or stereotactic radiosurgery.
• •At least 2 weeks must have elapsed since the completion of radiotherapy at any site other than brain, prior to start of study medication. At least 4 weeks must have elapsed since the completion of brain radiotherapy.
• •At least 4 weeks must have elapsed since systemic therapy prior to start of study medication, all clinically significant toxicities (other than hair loss) must have resolved, and the patient must meet the eligibility criteria.
• •Systemic disease may be absent, present and controlled or present and uncontrolled. If uncontrolled, the systemic disease should be considered less life-threatening than the cerebral disease. Patients may have received adjuvant chemotherapy and may have received one or more chemotherapy regimens for metastatic disease.
• •Patients with breast cancer who have progressive brain metastases, but stable systemic disease whilst on hormonal therapy, may continue the same hormonal therapy, as it can be assumed that the blood brain barrier is preventing response to this agent in the central nervous system (CNS).
• •Bidimensionally measurable disease must be documented in the brain on gadolinium magnetic resonance imaging (GdMRI) scan of the brain within 14 days prior to enrollment into the study. In the case of patients who received prior radiotherapy, the MRI scan findings must be consistent with progressive disease following treatment.
• •Subjects who have had previous surgery or stereotactic radiotherapy must have lesions clearly measurable and distinct from the surgical and/or radiation changes induced by prior or local therapies.