A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors

Clin Cancer Res. 1999 Nov;5(11):3394-402.


Standard treatment for neoplastic meningitis requires frequent intrathecal (IT) injections of chemotherapy and is only modestly effective. DepoCyt is a sustained-release formulation of cytarabine that maintains cytotoxic concentrations of the drug in the cerebrospinal fluid (CSF) for more than 14 days after a single 50-mg injection. We conducted a randomized, controlled trial of DepoCyt versus methotrexate in patients with solid tumor neoplastic meningitis. Sixty-one patients with histologically proven cancer and positive CSF cytologies were randomized to receive IT DepoCyt (31 patients) or IT methotrexate (30 patients). Patients received up to six 50-mg doses of DepoCyt or up to sixteen 10-mg doses of methotrexate over 3 months. Treatment arms were well balanced with respect to demographic and disease-related characteristics. Responses occurred in 26% of DepoCyt-treated and 20% of methotrexate-treated patients (P = 0.76). Median survival was 105 days in the DepoCyt arm and 78 days in the methotrexate arm (log-rank P = 0.15). The DepoCyt group experienced a greater median time to neurological progression (58 versus 30 days; log-rank P = 0.007) and longer neoplastic meningitis-specific survival (log-rank P = 0.074; median meningitis-specific survival, 343 versus 98 days). Factors predictive of longer progression-free survival included absence of visible central nervous system disease on neuroimaging studies (P<0.001), longer pretreatment duration of CSF disease (P<0.001), history of intraparenchymal tumor (P<0.001), and treatment with DepoCyt (P = 0.002). The frequency and grade of adverse events were comparable between treatment arms. In patients with solid tumor neoplastic meningitis, DepoCyt produced a response rate comparable to that of methotrexate and significantly increased the time to neurological progression while offering the benefit of a less demanding dose schedule.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Breast Neoplasms / drug therapy
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Small Cell / drug therapy
  • Cytarabine / administration & dosage
  • Cytarabine / therapeutic use*
  • Delayed-Action Preparations
  • Disease Progression
  • Female
  • Humans
  • Injections, Spinal
  • Lung Neoplasms / drug therapy
  • Male
  • Melanoma / drug therapy
  • Meningeal Neoplasms / drug therapy*
  • Meningeal Neoplasms / mortality
  • Meningeal Neoplasms / secondary*
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Neoplasms / pathology
  • Prospective Studies
  • Survival Rate
  • Survivors


  • Antimetabolites, Antineoplastic
  • Delayed-Action Preparations
  • Cytarabine
  • Methotrexate