Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

K. A. Jaeckle, S. Phuphanich, M. J. Van den Bent, R. Aiken, T. Batchelor, T. Campbell, D. Fulton, M. Gilbert, D. Heros, L. Rogers, S. J. O'Day, W. Akerley, J. Allen, S. Baidas, S. Z. Gertler, H. S. Greenberg, S. LaFollette, G. Lesser, W. Mason, L. RechtE. Wong, M. C. Chamberlain, A. Cohn, M. J. Glantz, J. C. Gutheil, B. Maria, P. Moots, P. New, C. Russell, W. Shapiro, L. Swinnen, S. B. Howell

Research output: Contribution to journalArticlepeer-review

Abstract

Depocyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515 +); median survival was 88 days (range 1-515 +), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalBritish journal of cancer
Volume84
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Breast cancer
  • Cytarabine
  • Drug delivery
  • Neoplastic meningitis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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