Methotrexate and Thiotepa in Treating Patients With Newly Diagnosed Primary CNS Lymphoma

OBJECTIVES:

• Determine the complete radiographic response in patients with newly diagnosed primary CNS lymphoma treated with methotrexate and thiotepa.
• Determine the duration of progression-free survival and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine whether tumor expression of BCL-6 is associated with response to this chemotherapy regimen and survival of these patients.
• Describe the relationship between initial response to steroids (if administered), response to this chemotherapy regimen, and survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive thiotepa IV over 15 minutes on day 1. Patients also receive methotrexate IV over 4 hours on days 1 (8 hours after thiotepa) and 14. Beginning 24 hours after the start of methotrexate infusion, patients receive leucovorin calcium IV or orally every 6 hours until rescue is achieved. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving disappearance of enhancement of disease on MRI receive an additional 28-day course followed by maintenance therapy comprising thiotepa and methotrexate once a month for 11 courses.

Patients undergo neuro-ophthalmologic exams annually for 2 years.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 23-39 patients will be accrued for this study within 8-20 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary CNS lymphoma

• Confirmed by 1 of the following:

• Brain biopsy or resection
• CSF cytology

• Positive cytology or immunohistochemical diagnosis of monoclonality and measurable intracranial tumor
• Vitreal biopsy
• Measurable and contrast-enhancing disease on the postoperative, pretreatment MRI or CT scan
• No radiographic evidence of ascites or pleural effusions

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• SGOT no greater than 4 times upper limit of normal

Renal

• Creatinine no greater than 2 mg/dL
• Creatinine clearance at least 50 mL/min

Other

• Mini mental score of at least 15
• HIV negative
• Able to achieve hydration
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ
• No allergy to methotrexate
• No serious infection
• No medical illness that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy or biologic therapy for this disease

Chemotherapy

• No prior chemotherapy for this disease
• No other concurrent chemotherapeutic agents

Endocrine therapy

• No prior hormonal therapy for this disease
• Prior glucocorticoid therapy allowed

Radiotherapy

• No prior radiotherapy for this disease
• No prior cranial irradiation

Surgery

• See Disease Characteristics

Other

• At least 1 week since prior salicylates, non-steroidal anti-inflammatory drugs, probenecid, folic acid, or sulfonamide medications
• No other concurrent investigational agents