• Maximum tolerated dose as measured by NCI CTC v2 toxicities [ Designated as safety issue: Yes ]
  

• Efficacy of chemotherapy regimen as measured by clinical and radiographic response continuously from first day of treatment [ Designated as safety issue: No ]
  

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.

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