Survival of patients with high grade glioma treated with intrathecal thiotriethylenephosphoramide for ependymal or leptomeningeal gliomatosis

Abstract

Background: The diagnosis of leptomeningeal dissemination of malignant glioma (meningeal gliomatosis) is associated with poor survival. Intrathecal (IT) chemotherapeutic agents used to achieve tumor control and improve survival include methotrexate, cytosine arabinoside (ara-C), thiotriethylenephosphoramide (thio-TEPA), neocarzinostatin, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros ourea hydrochloride (ACNU). Little information exists about survival following administration of IT chemotherapy. The authors report survival data from a series of patients with supratentorial anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) treated for ependymal or leptomeningeal gliomatosis with IT thio-TEPA.

Methods: The authors reviewed the records of 14 patients treated between 1991 and 1997 (GBM: n = 9; AA: n = 5). All patients were diagnosed with ependymal (n = 8) or leptomeningeal (n = 6) dissemination of tumor on the basis of clinical signs and symptoms, ependymal or leptomeningeal contrast enhancement on magnetic resonance imaging (MRI), and/or cerebrospinal fluid analysis. All 14 patients underwent placement of a ventricular reservoir system and subsequent instillation of IT thio-TEPA on a weekly basis for 6-12 weeks. Response to treatment was evaluated clinically and by MRI at intervals of 1-3 months and 3-6 months from the initiation of IT thio-TEPA. Data on survival from the time of diagnosis of dissemination was assessed.

Results: The median survival, from the time of diagnosis of ependymal or leptomeningeal dissemination, of patients who received IT thio-TEPA was 10 months (AA = 19 months; GBM = 10 months). Five of 14 patients had a radiographic response to treatment within 6 months. The median survival of patients with a radiographic response was 15.5 months, compared with 10 months for nonresponders. No significant neurotoxicity or myelopathy was observed.

Conclusions: Early treatment with IT thio-TEPA may result in improved survival with minimal morbidity. Radiographic response may predict prolonged survival.