Special Report

*Author for correspondence:

E-mail Address: archit.baskaran@uchicagomedicine.org

https://orcid.org/0000-0002-1729-0142

Resident, Department of Neurology, The University of Chicago Medicine, Chicago, IL 60637, USA

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Ankush Bhatia

https://orcid.org/0000-0001-5292-2822

Section Head of Neuro-Oncology, Department of Neurology, Medicine, & Human Oncology, University of Wisconsin School of Medicine & Public Health, Madison, WI 53705, USA

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Priya Kumthekar

https://orcid.org/0000-0001-5923-0677

Department of Neurology, Lou & Jean Malnati Brain Tumor Institute, Northwestern University, Chicago, IL 60611, USA

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Adrienne Boire

https://orcid.org/0000-0002-9029-1248

Geoffrey Beene Junior Faculty Chair, Department of Neurology, Human Oncology & Pathogenesis Program, Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

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Rimas V Lukas

https://orcid.org/0000-0002-9352-5396

Neuro-Oncology Division, Associate Professor, Regional Ambulatory Medical Director, Neurology, Department of Neurology, Lou & Jean Malnati Brain Tumor Institute, Northwestern University, Chicago, IL 60611, USA

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Published Online:22 Sep 2023https://doi.org/10.2217/fon-2022-0926

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Abstract

Aims/purpose: Leptomeningeal metastases (LM) are associated with substantial morbidity and mortality. Several approaches are used to treat LM, including intrathecally administered therapies. We consolidated current studies exploring intrathecal therapies for LM treatment. Patients & methods: A review of clinical trials using intrathecal agents was conducted with outcomes tabulated and trends described. 48 trials met the inclusion criteria. Initial investigations began with cytotoxic agents; following this were formulations with longer cerebrospinal fluid half-lives, targeted antibodies and radionucleotides. Results & conclusion: Outcomes were not reported consistently. Survival, when reported, remained poor. Intrathecal therapies for LM remain a viable option. Their use can be informed by an understanding of efficacy, safety and toxicity. They may be an important component of future LM treatments.

Plain language summary

This paper summarizes the findings from 48 clinical trials conducted since the 1970s about the treatment of leptomeningeal metastases through an intrathecal approach (administering drugs directly into the cerebrospinal fluid – a fluid that surrounds the brain and spinal cord). The results of these studies suggest that although these therapies show promise for the future, they currently do not clearly and consistently report a benefit. Further work is needed to explore the possible use of these treatments.

Keywords:

Papers of special note have been highlighted as: • of interest

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Vol. 19, No. 26

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Received 17 September 2022

Accepted 10 August 2023

Published online 22 September 2023

Published in print August 2023

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To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2022-0926

Financial & competing interests disclosure

R Lukas: speakers’ bureau for Merck, speakers’ bureau for Novocure, scientific advisory board for Merck, research support (drug only) from BMS. P Kumthekar reports consulting fees from Biocept, Affinia, Enclear, Angiochem, Bioclinica; payment or honoraria from Novocure, Sintetica; patents: European Patent 3307327, 12 August 2020; US Patent Pending 15/737, 188; participation on a Data Safety Monitoring Board or Advisory Board for Berg, Janssen, Mirati, Orbus Therapeutics, Celularity, SDP Oncology; and stock or stock options for Enclear. A Boire reports the following patents: Boire A and J Massagué, inventors, Sloan Kettering Institute, assignee – Modulating Permeability of The Blood Cerebrospinal Fluid Barrier, United States Provisional Application No.: 62/258,044, 20 November 2015; Boire A, Chen Q and J Massagué, inventors, Sloan Kettering Institute, assignee – Methods for Treating Brain Metastasis, United States Patent number 10413522, 17 September 2019; Boire A and Y Chi, inventors, Sloan Kettering Institute, assignee – Methods for Treating Leptomeningeal Metastasis, United States Provisional Application No.: 63/052,139, 15 July 2020. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Cerebrospinal fluid-administered therapies for leptomeningeal metastases from solid tumors

Abstract

Plain language summary

References