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The efficacy of slow-rate ventriculolumbar perfusion chemotherapy for leptomeningeal carcinomatosis: a phase II study

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Abstract

Purpose

This study aimed to evaluate the symptomatic response and side effects of ventriculolumbar perfusion (VLP) methotrexate chemotherapy with a low perfusion rate in patients with leptomeningeal metastasis.

Methods

Patients in a single-arm, two-stage phase II trial based on Simon’s minimax design received VLP with a reduced (15 cc/h) perfusion rate with the purpose of decreasing constitutional side effects such as nausea/vomiting, insomnia, and confusion. The primary outcome was control of increased intracranial pressure (ICP). The secondary outcome was an occurrence of side effects. The results were compared with those of a previous trial of VLP with a 20-cc/h perfusion rate.

Results

Total 90 patients were enrolled. Out of 65 patients with increased ICP, 32 achieved normalized ICP after VLP chemotherapy (bias-adjusted response rate = 51%). The incidence of moderate-to-severe nausea/vomiting was reduced to 46% from 64% in the previous study, and that of sleep disturbance was increased to 13% from 9%, but both failed to reach statistical significance. The incidence of moderate-to-severe confusion was significantly reduced to 12% from 23% in the previous study (p = 0.04). Median overall survival was better among patients with controlled ICP than among those who remained with increased ICP (193 days vs. 94 days, p = 0.013).

Conclusion

Compared with a higher perfusion rate, the low perfusion rate failed to provide non-inferior ICP control or improved side effects, except for confusion. The relationship between VLP perfusion rate and ICP control needs to be evaluated in future trials adjusting for bias from uncompleted protocol due to poor general condition.

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Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information.

Code availability

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Funding

This work was supported by a grant (2210650–2) from the National Cancer Center, Korea, and the Korea Health Industry Development Institute of the Ministry of Health and Social Welfare, Republic of Korea (H1731340-1). The sponsor had no role in the design or conduct of this research.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea

    Soojin Jang

  2. Department of Cancer Control, Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-Ro, Ilsandong-Gu, Goyang, Korea

    Ho-Shin Gwak

  3. Biometric Research Branch, National Heart, Lung and Blood Institute, Bethesda, USA

    Jungnam Joo

  4. Neuro-Oncology Clinic, National Cancer Center, Goyang, Korea

    Yoon-Sik Doh, Sang-Hoon Shin, Heon Yoo & Kyu-Chang Wang

Authors
  1. Soojin Jang
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  5. Sang-Hoon Shin
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Contributions

Conceptualization and design: HSG. Data curation: SJ, HSG. Analysis and interpretation of the data: HSG, JJ. Writing – original draft: SJ, HSG. Writing—review & editing: all the authors.

Corresponding author

Correspondence to Ho-Shin Gwak.

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Ethics approval

All the procedures involving human participants were performed in accordance with the Institutional Review Board of the National Cancer Center of Korea (NCC2014-0061). The trial was registered on the government-owned official trial registration site (http://cris.nih.go.kr) before patient enrollment (KCT0000082) and was conducted according to the guidelines of the Declaration of Helsinki for biomedical research.

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Jang, S., Gwak, HS., Joo, J. et al. The efficacy of slow-rate ventriculolumbar perfusion chemotherapy for leptomeningeal carcinomatosis: a phase II study. Acta Neurochir 166, 117 (2024). https://doi.org/10.1007/s00701-024-05989-0

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