RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who
have leptomeningeal metastases from a solid tumor or lymphoma.
- Determine the objective response rate, survival time, and quality of life of patients
with leptomeningeal metastases from a solid tumor or lymphoma when treated with oral
- Determine adverse events related to this regimen in this patient population.
- Measure temozolomide concentrations in CSF and serum and correlate with appropriate
pharmacodynamic parameters (e.g., response) in these patients.
OUTLINE: Patients receive oral temozolomide daily for 6 weeks. Courses repeat every 10 weeks
in the absence of unacceptable toxicity or disease progression.
Patients with a complete response (CR) receive 2 additional courses after achieving CR.
Patients with a CR except for residual radiographic abnormalities that persist unchanged for
2 full courses continue for 4 courses past best response.
Quality of life is assessed at baseline, weekly for the first 4 weeks of therapy, and then
PROJECTED ACCRUAL: A total of 14-24 patients will be accrued for this study.
- Documented leptomeningeal metastases
- Carcinomatous meningitis that is previously untreated or failed prior therapy OR
- Lymphomatous meningitis
- Systemic disease that is responding or stable on current therapy not eligible if
discontinuing therapy would be deleterious
- Age 18 and over
- Karnofsky Performance Status 60-100%
- Life expectancy of at least 6 weeks
- Absolute neutrophil count greater than 1,500/μL
- Platelet count greater than 100,000/μL
- Creatinine no greater than 2.0 mg/dL
- No congestive heart failure
- No unstable angina
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No contraindication to diagnostic sampling of CSF via lumbar puncture or reservoir
- No medical conditions that would interfere with absorption of oral medication (e.g.,
malabsorption, obstruction, or frequent vomiting)
- No uncontrolled infection
- Prior neuroaxis chemotherapy (lumbar puncture, reservoir, or systemic) allowed
- No other concurrent chemotherapy for other sites of disease
- No prior radiotherapy to areas of measurable meningeal disease unless there is clear
radiographic progression in these areas
- No prior radiotherapy to greater than 30% of bone marrow
- Prior radiotherapy to the neuroaxis allowed
- No concurrent radiotherapy for other sites of disease or for progressive disease
- Recovered from any prior recent therapy