Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis.

Abstract

BACKGROUND:

A study was undertaken to determine whether route (intraventricular vs intralumbar) of intracerebrospinal fluid (intra-CSF) drug administration influences progression-free survival in the treatment of patients with neoplastic meningitis, which occurs in 1% to 5% of patients with known cancer. Currently available treatment options result in modest responses, which is in part a reflection of obstacles to drug delivery into the leptomeningeal space.

METHODS:

One hundred patients with clinically and cytologically or radiographically documented neoplastic meningitis because of solid cancers received intra-CSF liposomal cytarabine or methotrexate as specified in a randomized phase 4 trial. The 2 treatment arms were well balanced for demographic and tumor-related characteristics of known prognostic importance, including age, performance status, tumor type, extent of systemic and other central nervous system (CNS) disease, prior CNS therapy, and concurrent systemic chemotherapy.

RESULTS:

One hundred patients were randomized and treated (52 with sustained-release cytarabine, and 48 with methotrexate). Progression-free survival (the primary study endpoint) was identical between the sustained-release cytarabine and methotrexate treatment arms for all 100 patients (35 vs 37.5 days, P = .79). When progression-free survival was examined as a function of route of chemotherapy administration (lumbar vs ventricular), there was no difference for patients treated with sustained-release cytarabine (29 vs 43 days, P = .35). For patients treated with methotrexate, however, there was a statistically significant difference favoring patients receiving intraventricular therapy (19 vs 43 days, P = .048).

CONCLUSIONS:

Site of intra-CSF chemotherapy drug administration is clinically relevant with short half-life drugs such as methotrexate.

• Authors: Michael J Glantz, Alixis Van Horn, Rebecca Fisher, Marc C Chamberlain
• Journal: Cancer (Cancer) Vol. 116 Issue 8 Pg. 1947-52 (Apr 15 2010) ISSN: 0008-543X [Print] United States
• PMID: 20151421 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 American Cancer Society.

Chemical References

• Delayed-Action Preparations
• Cytarabine
• Methotrexate

Topics

• Adult
• Cytarabine (administration & dosage)
• Delayed-Action Preparations (administration & dosage)
• Disease-Free Survival
• Humans
• Injections, Intraventricular
• Meningeal Carcinomatosis (drug therapy)
• Meningitis (drug therapy)
• Methotrexate (administration & dosage)
• Neoplasms (complications)
• Spinal Puncture