Abstract

Malignant leptomeningeal dissemination poses significant treatment challenges and is difficult to eradicate. The disadvantages of conventional chemotherapy and intrathecal anticancer agents are due to limited drug penetration through the blood-brain barrier, low cytotoxic concentrations in the cerebrospinal fluid (CSF), and rapid metabolism. DepoCyte is a new liposomal, slow-release preparation of cytarabine for intrathecal use that maintains cytotoxic concentrations for as long as 14 days or more and improves the distribution of free cytarabine in the CSF.

Here, we report our experience concerning thirteen pediatric patients age 1–13 years who received more than 40 treatment doses with liposomal cytarabine either as a therapeutic or prophylactic agent in doses of either 35 mg or 50 mg (children 11 years and younger or 12 years and older, respectively). There were four patients with refractory/relapsing neuroblastoma stage IV, two of whom had confirmed central nervous system (CNS) involvement; and nine patients with CNS- and/or refractory/recurrent leukemia, including ALL, AML and infant ALL. Todate, individual patients have been treated with one to ten liposomal cytarabine doses each (medium 3,1), and one patient has received therapy over a period of one year (ten doses).

Patients were given arachnoiditis prophylaxis with either oral dexamethasone 0,15 mg/kg × 2 daily (max 4 mg per dose) for 5 days or intrathecal prednisolone in age-dependent doses (Precortalon Aquosum; 8 mg, 12,5 mg, and 15 mg for patients 1–2 years, 3–11 years, and 12 years and older, respectively). The intrathecal prednisolone that was given concomitantly with liposomal cytarabine in approximately half of the treatment doses. Was convenient and caused less side-effects than oral dexamethasone.

DepoCyte was well tolerated in most patients, but side-effects such as headache, nausea and vomiting occurred on four occasions. One patient had seizures in connection with high-dose intravenous cytarabine therapy.

We conclude, that intrathecal DepoCyte therapy in doses of 35 to 50 mg with concomitant oral or intrathecal steroids is a practical, safe, and well tolerated treatment for leptomeningeal malignant disease. Further research is needed to determine the long-term effects and side-effects.

Disclosure: No relevant conflicts of interest to declare.

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