OBJECTIVES:

• Determine the maximum tolerated dose of intrathecal busulfan by a limited escalation dosage schedule in patients with recurrent or refractory leptomeningeal tumors.
• Determine the cerebrospinal fluid and serum pharmacokinetics of busulfan administered via intralumbar or intraventricular routes in these patients.

OUTLINE: This is dose-escalation study.

Patients receive intrathecal busulfan via intralumbar or intraventricular routes twice a week for 2 weeks (4 treatments). Any patient with objective or significant clinical response may continue treatment by receiving the same dose once a week for 2 consecutive weeks, once a week every other week for 3 weeks (2 treatments), and then once a month thereafter until disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of intrathecal busulfan 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.

Patients are followed every 12 weeks for 1 year or until disease progression.

PROJECTED ACCRUAL: A total of 5-20 patients will be accrued for this study within 1-2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed neoplasm that is metastatic in the cerebrospinal fluid or leptomeningeal/subarachnoid space

  • Cytologic diagnosis of malignancy in the cerebrospinal fluid or neuroimaging evidence of leptomeningeal tumor by MRI

• Must have a recurrent or refractory leptomeningeal tumor

  • Leptomeningeal tumors of leukemia, lymphoma, and all germ cell tumors must have also failed initial treatment or be recurrent
• No evidence of obstructive hydrocephalus or complete block of the spinal cerebrospinal fluid pathways on prestudy technetium Tc 99m albumin or indium In 111 DTPA flow study

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 2.5 mg/dL
• SGOT or SGPT less than 1.5 times normal

Renal:

• BUN less than 30 mg/dL
• Creatinine less than 1.5 mg/dL
• Calcium within normal limits

Neurological:

• Neurological examination stable
• No rapidly progressing or deteriorating neurological deficits

Other:

• No active infectious process
• Magnesium, phosphorus, potassium, chloride, and bicarbonate normal
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy

Chemotherapy:

• At least 6 weeks since prior nitrosoureas or mitomycin
• At least 4 weeks since any other prior chemotherapy
• At least 3 weeks since prior intrathecal chemotherapy
• No other concurrent intrathecal chemotherapy

Endocrine therapy:

• For patients on corticosteroids:

  • Must be on a stable dose of corticosteroids for at least 1 week

Radiotherapy:

• At least 3 weeks since prior radiotherapy to the CNS
• At least 4 weeks since any other prior radiotherapy
• No concurrent radiotherapy to the CNS

Surgery:

• At least 3 weeks since prior surgery

Other:

• No concurrent medication that may interfere with study results (e.g., immunosuppressive agents other than corticosteroids)