title: A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors.
abstract: 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.
authors.affiliation: Department of Medicine, Brown University School of Medicine, Providence, Rhode Island 02860, USA. mjg@massmed.org
authors.forename: M J
authors.initials: MJ
authors.lastname: Glantz
authors.forename: K A
authors.initials: KA
authors.lastname: Jaeckle
authors.forename: M C
authors.initials: MC
authors.lastname: Chamberlain
authors.forename: S
authors.initials: S
authors.lastname: Phuphanich
authors.forename: L
authors.initials: L
authors.lastname: Recht
authors.forename: L J
authors.initials: LJ
authors.lastname: Swinnen
authors.forename: B
authors.initials: B
authors.lastname: Maria
authors.forename: S
authors.initials: S
authors.lastname: LaFollette
authors.forename: G B
authors.initials: GB
authors.lastname: Schumann
authors.forename: B F
authors.initials: BF
authors.lastname: Cole
authors.forename: S B
authors.initials: SB
authors.lastname: Howell
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D018450:Disease Progression; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology; D011446:Prospective Studies; D015996:Survival Rate; D017741:Survivors
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D003561:Cytarabine; D008727:Methotrexate