Pharmacologic Study of Methotrexate in Patients Undergoing Stereotactic Biopsy for Recurrent High-Grade Glioma

OBJECTIVES:

• Determine the feasibility of using microdialysis to study distribution of systemically administered methotrexate in the interstitial fluid within a tumor in patients undergoing stereotactic biopsy for recurrent high-grade gliomas.
• Determine the systemic and intratumoral pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients have an intratumoral microdialysis catheter placed while undergoing stereotactic biopsy. Between 18-32 hours after placement of catheter, patients receive methotrexate IV over 4 hours. Microdialysis perfusate and blood specimens are collected before, during, and for 24 hours after methotrexate administration.

Patients are followed at 2 weeks.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 6 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial grade III or IV astrocytoma of 1 of the following subtypes:

• Anaplastic astrocytoma
• Anaplastic oligodendroglioma
• Glioblastoma multiforme
• Measurable, contrast-enhancing, residual disease by MRI or CT scan
• Undergoing stereotactic biopsy for confirmation of tumor progression or differentiation of tumor progression from treatment-induced effects

• Patients with prior low-grade glioma that progressed after prior radiotherapy with or without chemotherapy and in need of stereotactic biopsy to confirm high-grade glioma are eligible
• Must have received prior radiotherapy with or without chemotherapy
• Planning to continue methotrexate therapy after participation on this study
• No ascites or pleural effusions

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 2.0 mg/dL
• SGOT ≤ 4 times upper limit of normal
• Creatinine ≤ 2 mg/dL
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ
• Able to achieve hydration necessary for the use of methotrexate
• Mini mental state exam score at least 15
• No allergy to methotrexate
• No other concurrent infection or medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• At least 3 months since prior radiotherapy
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• At least 1 week since prior salicylates, nonsteroidal anti-inflammatory drugs, or sulfonamides
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
• No concurrent chemotherapeutic agents
• No other concurrent investigational agents