A Phase II Study Of Systemic High-Dose Methotrexate For The Treatment Of Glioblastoma Multiforme In Newly Diagnosed Patients With Measurable Disease

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed glioblastoma multiforme (GBM)

- Supratentorial grade IV disease

- Measurable and contrast-enhancing disease ≥ 1 cm by CT scan or MRI

- No radiographic evidence of ascites or pleural effusion

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- SGOT ≤ 4.0 times upper limit of normal

- Bilirubin ≤ 2.0 mg/dL

Renal

- Creatinine ≤ 2.0 mg/dL

- Creatinine clearance ≥ 50 mL/min

Cardiovascular

- No uncontrolled hypertension

- No unstable angina

- No symptomatic congestive heart failure

- No uncontrolled cardiac arrhythmia

- No myocardial infarction within the past 6 months

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to achieve hydration

- No diabetes insipidus

- No known hypersensitivity to methotrexate or leucovorin calcium

- No concurrent serious infection or medical illness that would preclude study
participation

- No other malignancy within the past 2 years except basal cell or squamous cell skin
cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior immunotherapy for GBM

- No prior administration of any of the following biologic agents for GBM:

- Immunotoxins

- Immunoconjugates

- Antisense therapy

- Peptide receptor antagonists

- Interferons

- Interleukins

- Tumor-infiltrating lymphocytes

- Lymphokine-activated killer cells

- Gene therapy

- No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim
[GM-CSF])

Chemotherapy

- No prior chemotherapy for GBM

- No other concurrent chemotherapy

Endocrine therapy

- Prior glucocorticoid therapy allowed

- No prior hormonal therapy for GBM

- Patients must be maintained on a stable corticosteroid regimen for at least 1 week

Radiotherapy

- No prior cranial irradiation

- No prior radiotherapy for GBM

Surgery

- Recovered from prior surgery

Other

- At least 1 week since prior treatment with any of the following:

- Salicylates

- Non-steroidal anti-inflammatory drugs

- Sulfonamide medications

- Vitamin C

- No other concurrent investigational agents