Intrathecal cytosine arabinoside for the treatment of meningeal metastases from malignant brain tumors and systemic tumors

Summary Thirty-two patients with primary or metastatic neoplasms in the ventricular system or subarachnoid space were treated with intrathecal Ara-C. Twenty patients (group I) were treated with single twice-weekly doses; the mean number of doses was 9.7, and the mean total dosage was 165 mg. Six patients received intrathecal Ara-C alone and 14 received concurrent chemotherapy. All four symptomatic patients showed clinical improvement. Malignant cells disappeared from the spinal fluid of six of the 12 patients with positive pretherapy cerebrospinal fluid (CSF) cytology. Two patients were alive with no evidence of recurrence 8 and 16 weeks after beginning therapy, two patients died without demonstrating evidence of recurrence 8 weeks and 9 weeks after starting therapy, 12 patients had recurrences an average of 13 weeks after beginning treatment, and four patients refused further investigation or treatment and died of disease after 6–52 weeks.Pharmacokinetic studies were performed in eight patients. For five patients who received 12 mg Ara-C by injection into an SC-implanted reservior connected to the ventricular system, the CSF disappearance curve was biphasic with half-times of 30 min and 3.5 h.Based on the results of the pharmacokinetic study, an additional 12 patients (group II) were treated on three consecutive days weekly. The mean number of doses was 9.7 and the mean total dosage was 189 mg. Three patients received intrathecal Ara-C alone and nine received concurrent chemotherapy. One of the five symptomatic patients showed clinical improvement. Malignant cells disappeared from the spinal fluid of two of the four patients with positive pretherapy CSF cytology. Four patients were alive with no evidence of recurrence 3–26 weeks after beginning therapy, two patients died within 10 days of beginning treatment without formal re-evaluation, four patients demonstrated progression of tumor an average of 7 weeks after beginning treatment, and two patients changed to another form of therapy because of persistent CSF abnormalities, although there was no radiographic evidence of tumor progression.There were no clear differences in response between group I and group II; however, the groups were not comparable with respect to pathological diagnosis.Intrathecal Ara-C is a promising and relatively safe treatment for malignant disease in the subarachnoid space. Further studies are needed to determine the optimum dose and administration schedule in combination with other intrathecal therapies that may be more active against noncycling G₀ cells.