Temozolomide in Treating Patients With Leptomeningeal Metastases From a Solid Tumor or Lymphoma
Temozolomide in Treating Patients With Leptomeningeal Metastases From a Solid Tumor or Lymphoma
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.
OBJECTIVES:

 -  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
 temozolomide.

 -  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
 monthly thereafter.

 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