An open label trial of sustained-release cytarabine (DepoCyt™) for the intrathecal treatment of solid tumor neoplastic meningitis

Kurt A. Jaeckle, Tracy Batchelor, Steven J. O'Day, Surasak Phuphanich, Pamela New, Glenn Lesser, Allen Cohn, Mark Gilbert, Robert Aiken, Deborah Heros, Lisa Rogers, Eric Wong, Dorcas Fulton, John C. Gutheil, Said Baidas, Julia M. Kennedy, Warren Mason, Paul Moots, Christy Russell, Lode J. SwinnenStephen B. Howell

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90 Scopus citations

Abstract

Drugs currently available for intrathecal administration are cleared rapidly from the CSF. DepoCyt is a slow-release formulation of cytarabine that maintains cytotoxic concentrations of free cytarabine in the CSF for > 14 days following a single injection. DepoCyt was administered to 110 patients with a diagnosis of neoplastic meningitis based on either a positive CSF cytology (76) or neurologic and CT or MRI scan findings sufficient to document neoplastic meningitis (34). Patients were treated with DepoCyt 50 mg every 2 weeks for 1 month of induction therapy by either lumbar puncture (LP) or intraventricular (IVT) injection. Patients without neurologic progression were candidates to receive an additional 3 months of consolidation therapy. All patients received dexamethasone 4 mg BID on days 1-5 of each cycle. Median time to neurologic progression was 55 days; median overall survival was 95 days. Among the 76 patients with a positive CSF cytology at baseline, 70 were evaluable for response, and of this group19 (27%) attained the criteria for response (cytologic response in the absence of neurologic progression). The most important adverse events were headache and arachnoiditis. When drug-related, these were largely low grade, transient, and reversible. Drug-related grade 3 headache occurred on 4% of cycles; grade 3 or 4 arachnoiditis occurred on 6% of cycles. No cumulative toxicity was observed. DepoCyt injected once every 2 weeks produced a response-rate comparable to that previously reported for methotrexate given twice a week. The once in every 2-week-dosing interval offers an advantage over conventional schedules (2-3 doses/week) used for other agents available for intrathecal injection.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalJournal of Neuro-Oncology
Volume57
Issue number3
DOIs
StatePublished - 2002

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Keywords

  • Cerebrospinal fluid
  • Cytarabine
  • Intrathecal
  • Liposome
  • Neoplastic meningitis

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Jaeckle, K. A., Batchelor, T., O'Day, S. J., Phuphanich, S., New, P., Lesser, G., Cohn, A., Gilbert, M., Aiken, R., Heros, D., Rogers, L., Wong, E., Fulton, D., Gutheil, J. C., Baidas, S., Kennedy, J. M., Mason, W., Moots, P., Russell, C., ... Howell, S. B. (2002). An open label trial of sustained-release cytarabine (DepoCyt™) for the intrathecal treatment of solid tumor neoplastic meningitis. Journal of Neuro-Oncology, 57(3), 231-239. https://doi.org/10.1023/A:1015752331041