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

Michael J. Glantz, Kurt Jaeckle, Marc C. Chamberlain, Surasak Phuphanich, Lawrence Recht, Lode J. Swinnen, Bernard Maria, Susan LaFollette, G. Berry Schumann, Bernard F. Cole, Stephen B. Howell

Research output: Contribution to journalArticle

374 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3394-3402
Number of pages9
JournalClinical Cancer Research
Volume5
Issue number11
StatePublished - Nov 1 1999

Fingerprint

Cytarabine
Meningitis
Methotrexate
Randomized Controlled Trials
Neoplasms
Cerebrospinal Fluid
Survival
Spinal Injections
Central Nervous System Diseases
Therapeutics
Neuroimaging
Disease-Free Survival
Cell Biology
Appointments and Schedules
Demography
Drug Therapy
Injections
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Glantz, M. J., Jaeckle, K., Chamberlain, M. C., Phuphanich, S., Recht, L., Swinnen, L. J., ... Howell, S. B. (1999). A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clinical Cancer Research, 5(11), 3394-3402.
Glantz, Michael J. ; Jaeckle, Kurt ; Chamberlain, Marc C. ; Phuphanich, Surasak ; Recht, Lawrence ; Swinnen, Lode J. ; Maria, Bernard ; LaFollette, Susan ; Schumann, G. Berry ; Cole, Bernard F. ; Howell, Stephen B. / A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 11. pp. 3394-3402.
@article{460fd7249a2b412499b079b0ee914828,
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.",
author = "Glantz, {Michael J.} and Kurt Jaeckle and Chamberlain, {Marc C.} and Surasak Phuphanich and Lawrence Recht and Swinnen, {Lode J.} and Bernard Maria and Susan LaFollette and Schumann, {G. Berry} and Cole, {Bernard F.} and Howell, {Stephen B.}",
year = "1999",
month = "11",
day = "1",
language = "English (US)",
volume = "5",
pages = "3394--3402",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

Glantz, MJ, Jaeckle, K, Chamberlain, MC, Phuphanich, S, Recht, L, Swinnen, LJ, Maria, B, LaFollette, S, Schumann, GB, Cole, BF & Howell, SB 1999, 'A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors', Clinical Cancer Research, vol. 5, no. 11, pp. 3394-3402.

A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. / Glantz, Michael J.; Jaeckle, Kurt; Chamberlain, Marc C.; Phuphanich, Surasak; Recht, Lawrence; Swinnen, Lode J.; Maria, Bernard; LaFollette, Susan; Schumann, G. Berry; Cole, Bernard F.; Howell, Stephen B.

In: Clinical Cancer Research, Vol. 5, No. 11, 01.11.1999, p. 3394-3402.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors

AU - Glantz, Michael J.

AU - Jaeckle, Kurt

AU - Chamberlain, Marc C.

AU - Phuphanich, Surasak

AU - Recht, Lawrence

AU - Swinnen, Lode J.

AU - Maria, Bernard

AU - LaFollette, Susan

AU - Schumann, G. Berry

AU - Cole, Bernard F.

AU - Howell, Stephen B.

PY - 1999/11/1

Y1 - 1999/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032711629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032711629&partnerID=8YFLogxK

M3 - Article

C2 - 10589750

AN - SCOPUS:0032711629

VL - 5

SP - 3394

EP - 3402

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 11

ER -