RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving drugs directly into the arteries around the tumor may kill more tumor cells. Mannitol may open the blood vessels around the brain and allow melphalan to be carried directly to the brain. Giving melphalan together with mannitol may be an effective treatment for central nervous system cancer.

PURPOSE: This phase I trial is studying side effects and best dose of melphalan when given together with mannitol in treating patients with central nervous system cancer.

OBJECTIVES:

• Determine the maximum tolerated dose of intra-arterial melphalan when given in combination with mannitol in patients with primary or metastatic CNS malignancy.
• Determine the toxic effects of this regimen in these patients.
• Determine, preliminarily, the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of melphalan.

Patients receive intra-arterial mannitol followed by melphalan over 10 minutes on days 1 and 2*. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients with gliomas localized to the posterior circulation (i.e., brain stem gliomas) receive melphalan on day 1 only.

Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study therapy, patients are followed periodically for at least 1 year.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

• Brain and Central Nervous System Tumors
• Chordoma
• Lymphoma
• Metastatic Cancer
• Von Hippel-Lindau Syndrome

• Drug: mannitol
• Drug: melphalan

DISEASE CHARACTERISTICS:

• Histologically confirmed primary or metastatic CNS malignancy

  • Patients with metastatic disease must have histological confirmation of the primary cancer AND confirmation by surgical specimen, cerebrospinal fluid cytology, elevated tumor markers, or clinical evidence of CNS involvement
• Single or multiple cerebellar or cerebral cortex lesions allowed
• Radiographically evaluable disease by MRI or CT scan
• Other tumor masses in the spinal cord allowed provided there is no radiographic or clinical evidence of spinal cord block
• No radiographic evidence of uncal herniation

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• At least 60 days

Hematopoietic

• WBC > 2,500/mm^3
• Absolute granulocyte count > 1,200/mm^3
• Platelet count > 100,000/mm^3
• Hematocrit > 30% (transfusion allowed)

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• SGOT ≤ 3 times ULN

Renal

• Creatinine ≤ 2 times ULN

Cardiovascular

• Adequate cardiac function

Pulmonary

• Adequate pulmonary function
• DLCO ≥ 80% of predicted for patients with prior smoking history or emphysema

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 2 months prior to*, during, and for 3 months after study participation
• Able to tolerate general anesthesia
• No known hypersensitivity or intolerance to melphalan
• No grade 3 or greater baseline neurologic symptoms
• Not immunologically compromised
• No known HIV positivity
• No other serious illness that would preclude study participation [Note: *This criterion may be waived at the discretion of the investigator for patients with life-threatening tumors for which the 2-month wait would not be feasible]

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• At least 28 days since prior chemotherapy (42 days for nitrosoureas)

Endocrine therapy

• Concurrent corticosteroids for tumor edema allowed

Radiotherapy

• At least 28 days since prior radiotherapy (systemic, cranial, and/or spinal)
• No concurrent radiotherapy