RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Giving drugs into the thin space between the lining of the
spinal cord and brain may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of intrathecal busulfan in treating
patients with recurrent, refractory, or metastatic leptomeningeal tumors.
- 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.
- Histologically confirmed neoplasm that is metastatic in the cerebrospinal fluid or
- 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
- 18 and over
- Karnofsky 60-100%
- At least 8 weeks
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count greater than 100,000/mm^3
- Bilirubin less than 2.5 mg/dL
- SGOT or SGPT less than 1.5 times normal
- BUN less than 30 mg/dL
- Creatinine less than 1.5 mg/dL
- Calcium within normal limits
- Neurological examination stable
- No rapidly progressing or deteriorating neurological deficits
- No active infectious process
- Magnesium, phosphorus, potassium, chloride, and bicarbonate normal
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior immunotherapy
- 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
- For patients on corticosteroids:
- Must be on a stable dose of corticosteroids for at least 1 week
- 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
- At least 3 weeks since prior surgery
- No concurrent medication that may interfere with study results (e.g.,
immunosuppressive agents other than corticosteroids)