Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis

L. Bomgaars, J. R. Geyer, J. Franklin, G. Dahl, J. Park, N. J. Winick, R. Klenke, S. L. Berg, S. M. Blaney

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Purpose: We performed a phase I trial of intrathecal (IT) liposomal cytarabine (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego, CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children ≥ 3 years of age with advanced meningeal malignancies. Patients and Methods: Eighteen assessable patients received IT liposomal cytarabine through either an indwelling ventricular access device or via lumbar puncture. Liposomal cytarabine was given once every 2 weeks during induction, once every 4 weeks during consolidation, and once every 8 weeks during the maintenance phase of treatment. The initial dose was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic samples were obtained in a subset of patients. Results: Arachnoiditis, characterized by fever, headache, nausea, vomiting, and back pain was noted in the first two patients at the 25 mg dose level. Therefore, subsequent patients were treated with dexamethasone, beginning the day of liposomal cytarabine administration and continuing for 5 days. Headache (grade 3) was dose limiting in two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients assessable for response demonstrated evidence of benefit manifest as prolonged disease stabilization or response. Conclusion: The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development.

Original languageEnglish (US)
Pages (from-to)3916-3921
Number of pages6
JournalJournal of Clinical Oncology
Volume22
Issue number19
DOIs
StatePublished - 2004

Fingerprint

Cytarabine
Meningitis
Maximum Tolerated Dose
Dexamethasone
Headache
Pharmacokinetics
Arachnoiditis
Spinal Puncture
Back Pain
Nausea
Vomiting
Leukemia
Fever
Maintenance
Recurrence
Equipment and Supplies
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. / Bomgaars, L.; Geyer, J. R.; Franklin, J.; Dahl, G.; Park, J.; Winick, N. J.; Klenke, R.; Berg, S. L.; Blaney, S. M.

In: Journal of Clinical Oncology, Vol. 22, No. 19, 2004, p. 3916-3921.

Research output: Contribution to journalArticle

Bomgaars, L, Geyer, JR, Franklin, J, Dahl, G, Park, J, Winick, NJ, Klenke, R, Berg, SL & Blaney, SM 2004, 'Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis', Journal of Clinical Oncology, vol. 22, no. 19, pp. 3916-3921. https://doi.org/10.1200/JCO.2004.01.046
Bomgaars, L. ; Geyer, J. R. ; Franklin, J. ; Dahl, G. ; Park, J. ; Winick, N. J. ; Klenke, R. ; Berg, S. L. ; Blaney, S. M. / Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 19. pp. 3916-3921.
@article{1ce1d98c884e4fe3b098db640fed48c5,
title = "Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis",
abstract = "Purpose: We performed a phase I trial of intrathecal (IT) liposomal cytarabine (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego, CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children ≥ 3 years of age with advanced meningeal malignancies. Patients and Methods: Eighteen assessable patients received IT liposomal cytarabine through either an indwelling ventricular access device or via lumbar puncture. Liposomal cytarabine was given once every 2 weeks during induction, once every 4 weeks during consolidation, and once every 8 weeks during the maintenance phase of treatment. The initial dose was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic samples were obtained in a subset of patients. Results: Arachnoiditis, characterized by fever, headache, nausea, vomiting, and back pain was noted in the first two patients at the 25 mg dose level. Therefore, subsequent patients were treated with dexamethasone, beginning the day of liposomal cytarabine administration and continuing for 5 days. Headache (grade 3) was dose limiting in two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients assessable for response demonstrated evidence of benefit manifest as prolonged disease stabilization or response. Conclusion: The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development.",
author = "L. Bomgaars and Geyer, {J. R.} and J. Franklin and G. Dahl and J. Park and Winick, {N. J.} and R. Klenke and Berg, {S. L.} and Blaney, {S. M.}",
year = "2004",
doi = "10.1200/JCO.2004.01.046",
language = "English (US)",
volume = "22",
pages = "3916--3921",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "19",

}

TY - JOUR

T1 - Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis

AU - Bomgaars, L.

AU - Geyer, J. R.

AU - Franklin, J.

AU - Dahl, G.

AU - Park, J.

AU - Winick, N. J.

AU - Klenke, R.

AU - Berg, S. L.

AU - Blaney, S. M.

PY - 2004

Y1 - 2004

N2 - Purpose: We performed a phase I trial of intrathecal (IT) liposomal cytarabine (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego, CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children ≥ 3 years of age with advanced meningeal malignancies. Patients and Methods: Eighteen assessable patients received IT liposomal cytarabine through either an indwelling ventricular access device or via lumbar puncture. Liposomal cytarabine was given once every 2 weeks during induction, once every 4 weeks during consolidation, and once every 8 weeks during the maintenance phase of treatment. The initial dose was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic samples were obtained in a subset of patients. Results: Arachnoiditis, characterized by fever, headache, nausea, vomiting, and back pain was noted in the first two patients at the 25 mg dose level. Therefore, subsequent patients were treated with dexamethasone, beginning the day of liposomal cytarabine administration and continuing for 5 days. Headache (grade 3) was dose limiting in two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients assessable for response demonstrated evidence of benefit manifest as prolonged disease stabilization or response. Conclusion: The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development.

AB - Purpose: We performed a phase I trial of intrathecal (IT) liposomal cytarabine (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego, CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children ≥ 3 years of age with advanced meningeal malignancies. Patients and Methods: Eighteen assessable patients received IT liposomal cytarabine through either an indwelling ventricular access device or via lumbar puncture. Liposomal cytarabine was given once every 2 weeks during induction, once every 4 weeks during consolidation, and once every 8 weeks during the maintenance phase of treatment. The initial dose was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic samples were obtained in a subset of patients. Results: Arachnoiditis, characterized by fever, headache, nausea, vomiting, and back pain was noted in the first two patients at the 25 mg dose level. Therefore, subsequent patients were treated with dexamethasone, beginning the day of liposomal cytarabine administration and continuing for 5 days. Headache (grade 3) was dose limiting in two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients assessable for response demonstrated evidence of benefit manifest as prolonged disease stabilization or response. Conclusion: The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development.

UR - http://www.scopus.com/inward/record.url?scp=5444268197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=5444268197&partnerID=8YFLogxK

U2 - 10.1200/JCO.2004.01.046

DO - 10.1200/JCO.2004.01.046

M3 - Article

C2 - 15459213

AN - SCOPUS:5444268197

VL - 22

SP - 3916

EP - 3921

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 19

ER -