Subscribe to RSS
DOI: 10.1055/a-2185-0457
Intrathecal Therapy Options for Meningeal Carcinomatosis
Article in several languages: English | deutschAbstract
Around 5 percent of all patients with metastatic breast cancer go on to develop distant metastases in the meninges, also known as meningeal carcinomatosis. The median survival of these patients is between 3.5 and 4.5 months. Current treatment approaches are based on radiotherapy, systemic and intrathecal therapy. Methotrexate, liposomal cytarabine and trastuzumab are the most common substances used for intrathecal therapy. The aim of this review was to provide an overview of these intrathecal therapy options for meningeal carcinomatosis. A systematic search of the literature was carried out in PubMed using the following search terms: “meningeal metastases”, “meningeal carcinomatosis”, “leptomeningeal metastasis”, “leptomeningeal carcinomatosis”, “leptomeningeal disease”, “breast cancer”, “MTX”, “methotrexate”, “DepoCyte”, “liposomal cytarabine”, “trastuzumab” and “anti-HER2”. This search resulted in 75 potentially relevant studies, 11 of which were included in this review after meeting the previously determined inclusion and exclusion criteria. The studies differ considerably with regards to study design, cohort size, and dosages of administered drugs. In principle, intrathecal therapy has a tolerable side-effects profile and offers promising results in terms of the median overall survival following treatment with trastuzumab for HER2-positive primary tumors. The focus when treating meningeal carcinomatosis must be on providing a multimodal individual therapeutic approach. However, comprehensive studies which compare the efficacy and side effects of individual pharmaceuticals are lacking. Because of the poor prognosis associated with meningeal carcinomatosis, an approach which treats only the symptoms (best supportive care) should always be considered and discussed with affected patients.
Publication History
Received: 27 August 2023
Accepted after revision: 29 September 2023
Article published online:
08 November 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References/Literatur
- 1 Zentrum für Krebsregisterdaten, R.K.-I. Brustkrebs. 2019 Accessed September 07, 2022 at: https://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Brustkrebs/brustkrebs_node.html;jsessionid=2EA11A19A0F0B50977FADAF71B921254.internet102
- 2 Deutsche Krebsgesellschaft (DKG). Interdisziplinäre S3-Leitlinie für die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms. 2021 Accessed September 07, 2022 at: https://www.awmf.org/leitlinien/detail/ll/032–045OL.html
- 3 Mack F, Baumert BG, Schäfer N. et al. Therapy of leptomeningeal metastasis in solid tumors. Cancer Treat Rev 2016; 43: 83-91 DOI: 10.1016/j.ctrv.2015.12.004. (PMID: 26827696)
- 4 Chamberlain MC, Kormanik PR. Carcinomatous meningitis secondary to breast cancer: predictors of response to combined modality therapy. J Neurooncol 1997; 35: 55-64 DOI: 10.1023/a:1005803918194. (PMID: 9266441)
- 5 Rudnicka H, Niwińska A, Murawska M. Breast cancer leptomeningeal metastasis--the role of multimodality treatment. J Neurooncol 2007; 84: 57-62 DOI: 10.1007/s11060-007-9340-4. (PMID: 17310266)
- 6 Franzoi MA, Hortobagyi GN. Leptomeningeal carcinomatosis in patients with breast cancer. Crit Rev Oncol Hematol 2019; 135: 85-94 DOI: 10.1016/j.critrevonc.2019.01.020. (PMID: 30819451)
- 7 Niwińska A, Rudnicka H, Murawska M. Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival. Med Oncol 2013; 30: 408 DOI: 10.1007/s12032-012-0408-4. (PMID: 23322521)
- 8 de Azevedo CR, Cruz MR, Chinen LT. et al. Meningeal carcinomatosis in breast cancer: prognostic factors and outcome. J Neurooncol 2011; 104: 565-572 DOI: 10.1007/s11060-010-0524-y. (PMID: 21234642)
- 9 Lee S, Ahn HK, Park YH. et al. Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations. Breast Cancer Res Treat 2011; 129: 809-817 DOI: 10.1007/s10549-011-1682-0.
- 10 Arbeitsgemeinschaft Gynäkologische Onkologie, Kommission Mamma. Leitlinien & Empfehlungen ZNS Metastasen. 2023 Accessed July 16, 2023 at: https://www.ago-online.de/leitlinien-empfehlungen/leitlinien-empfehlungen/kommission-mamma
- 11 Bommer M, Bullinger L. Meningeosis carcinomatosa. Onkologe 2016; 22: 321-328 DOI: 10.1007/s00761-016-0011-y.
- 12 Laakmann E, Witzel I, Müller V. Efficacy of Liposomal Cytarabine in the Treatment of Leptomeningeal Metastasis of Breast Cancer. Breast Care (Basel) 2017; 12: 165-167 DOI: 10.1159/000464400. (PMID: 28785184)
- 13 Le Rhun E, Wallet J, Mailliez A. et al. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer. Neuro Oncol 2020; 22: 524-538 DOI: 10.1093/neuonc/noz201. (PMID: 31637444)
- 14 Jaeckle KA, Phuphanich S, Bent MJ. et al. Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine. Br J Cancer 2001; 84: 157-163 DOI: 10.1054/bjoc.2000.1574. (PMID: 11161370)
- 15 Zagouri F, Zoumpourlis P, Le Rhun E. et al. Intrathecal administration of anti-HER2 treatment for the treatment of meningeal carcinomatosis in breast cancer: A metanalysis with meta-regression. Cancer Treat Rev 2020; 88: 102046 DOI: 10.1016/j.ctrv.2020.102046. (PMID: 32599393)
- 16 Pappa E, Conforti R, Hoang-Xuan K. et al. Intrathecal Trastuzumab as a Potential Cause of Drug-Induced Aseptic Meningitis. Can J Neurol Sci 2019; 46: 358-359 DOI: 10.1017/cjn.2019.21. (PMID: 30905325)
- 17 Oberkampf F, Gutierrez M, Trabelsi Grati O. et al. Phase II study of intrathecal administration of trastuzumab in patients with HER2-positive breast cancer with leptomeningeal metastasis. Neuro Oncol 2023; 25: 365-374 DOI: 10.1093/neuonc/noac180. (PMID: 35868630)
- 18 Niwińska A, Rudnicka H, Murawska M. Breast cancer leptomeningeal metastasis: the results of combined treatment and the comparison of methotrexate and liposomal cytarabine as intra-cerebrospinal fluid chemotherapy. Clin Breast Cancer 2015; 15: 66-72 DOI: 10.1016/j.clbc.2014.07.004. (PMID: 25287959)
- 19 Meissner M, Addeo A. Intrathecal Methotrexate and Craniospinal Radiotherapy Can Be an Effective Treatment of Carcinomatous Meningitis in Patients with Breast Cancer: Case Reports. Case Rep Oncol 2016; 9: 586-592 DOI: 10.1159/000449448. (PMID: 27920689)
- 20 Gauthier H, Guilhaume MN, Bidard FC. et al. Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 2010; 21: 2183-2187 DOI: 10.1093/annonc/mdq232. (PMID: 20430906)
- 21 Freyer CW, Yaghmour G, Jennings K. et al. Drug-Induced Aseptic Meningitis Associated With Intrathecal Trastuzumab. J Pharm Technol 2014; 30: 43-47 DOI: 10.1177/8755122513500918. (PMID: 34860873)
- 22 Figura NB, Rizk VT, Mohammadi H. et al. Clinical outcomes of breast leptomeningeal disease treated with intrathecal trastuzumab, intrathecal chemotherapy, or whole brain radiation therapy. Breast Cancer Res Treat 2019; 175: 781-788 DOI: 10.1007/s10549-019-05170-7. (PMID: 30859348)
- 23 Carausu M, Carton M, Darlix A. et al. Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database. ESMO Open 2021; 6: 100150 DOI: 10.1016/j.esmoop.2021.100150. (PMID: 33984675)
- 24 Shapiro WR, Young DF, Mehta BM. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 1975; 293: 161-166 DOI: 10.1056/nejm197507242930402. (PMID: 806016)
- 25 Glantz MJ, Van Horn A, Fisher R. et al. Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis. Cancer 2010; 116: 1947-1952 DOI: 10.1002/cncr.24921. (PMID: 20151421)
- 26 Bonneau C, Paintaud G, Trédan O. et al. Phase I feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis. Eur J Cancer 2018; 95: 75-84 DOI: 10.1016/j.ejca.2018.02.032. (PMID: 29635147)
- 27 Klee GG, Tallman RD, Goellner JR. et al. Elevation of carcinoembryonic antigen in cerebrospinal fluid among patients with meningeal carcinomatosis. Mayo Clin Proc 1986; 61: 9-13 DOI: 10.1016/s0025-6196(12)61391-3. (PMID: 3510343)
- 28 Redaktion Gelbe Liste. Lieferengpass Depocyte. 2018 Accessed October 26, 2022 at: https://www.gelbe-liste.de/lieferengpaesse/lieferengpass-depocyte
- 29 Glitza Oliva IC, Ferguson SD, Bassett jr. R. et al. Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results. Nat Med 2023; 29: 898-905 DOI: 10.1038/s41591-022-02170-x. (PMID: 36997799)
- 30 Boogerd W, van den Bent M J, Koehler P J. et al. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer 2004; 40: 2726-2733 DOI: 10.1016/j.ejca.2004.08.012. (PMID: 15571954)
- 31 Witzel I, Laakmann E, Weide R. et al. Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry. Eur J Cancer 2018; 102: 1-9 DOI: 10.1016/j.ejca.2018.07.004. (PMID: 30099223)
- 32 Razis E, Escudero MJ, Palmieri C. et al. Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force. ESMO Open 2022; 7: 100483 DOI: 10.1016/j.esmoop.2022.100483. (PMID: 35576695)