Trabectedin has promising antineoplastic activity in high-grade meningioma

Authors

  • Matthias Preusser MD,

    1. Department of Medicine I, Medical University of Vienna, Vienna, Austria
    2. Comprehensive Cancer Center-Central Nervous System Tumors Unit, Medical University of Vienna, Vienna, Austria
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  • Sabine Spiegl-Kreinecker PhD,

    1. Department of Neurosurgery, Wagner-Jauregg Hospital, Linz, Austria
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  • Daniela Lötsch MS,

    1. Comprehensive Cancer Center-Central Nervous System Tumors Unit, Medical University of Vienna, Vienna, Austria
    2. Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria
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  • Adelheid Wöhrer MD,

    1. Comprehensive Cancer Center-Central Nervous System Tumors Unit, Medical University of Vienna, Vienna, Austria
    2. Institute of Neurology, Medical University of Vienna, Vienna, Austria
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  • Maria Schmook MD,

    1. Department of Radiology, Division of Neuroradiology, Medical University of Vienna, Vienna, Austria
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  • Karin Dieckmann MD,

    1. Comprehensive Cancer Center-Central Nervous System Tumors Unit, Medical University of Vienna, Vienna, Austria
    2. Department of Radiotherapy, Medical University of Vienna, Vienna, Austria
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  • Walter Saringer MD,

    1. Department of Neurosurgery, Medical University of Vienna, Vienna, Austria
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  • Christine Marosi MD,

    Corresponding author
    1. Department of Medicine I, Medical University of Vienna, Vienna, Austria
    2. Comprehensive Cancer Center-Central Nervous System Tumors Unit, Medical University of Vienna, Vienna, Austria
    • Department of Medicine I and Comprehensive Cancer Center-CNS Tumors Unit (CCC-CNS), Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

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    • Fax: (011) 43-1-40400-6088

  • Walter Berger PhD

    1. Comprehensive Cancer Center-Central Nervous System Tumors Unit, Medical University of Vienna, Vienna, Austria
    2. Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria
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Abstract

BACKGROUND:

Meningiomas are common intracranial tumors arising from the meninges and usually are benign. However, a few meningiomas have aggressive behavior and, for such patients, effective treatment options are needed. Trabectedin is a novel, marine-derived, antineoplastic agent that has been approved and is used routinely as therapy for advanced soft tissue sarcoma and ovarian cancer.

METHODS:

The authors investigated the in vitro effects of trabectedin alone and in combination with hydroxyurea, cisplatin, and doxorubicin in primary cell cultures of benign (n = 9), atypical (n = 6), and anaplastic (n = 4) meningiomas using chemosensitivity assays (3-[4,5dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT]), Western blot analysis, cell cycle analysis, and immunofluorescent staining.

RESULTS:

Strong antimeningioma activity of trabectedin was observed and was characterized by distinct cell cycle arrest, down-regulation of multiple cyclins, deregulated expression of cell death-regulatory genes, and massive apoptosis induction. Cytotoxic activity was especially intense in higher grade meningiomas with a half-maximal inhibitory concentration <10 nM. Combination with trabectedin synergistically enhanced the antimeningioma activity of hydroxyurea but also enhanced the activity of doxorubicin and cisplatin. On the basis of these findings, trabectedin was given to 1 patient who had heavily pretreated, anaplastic meningioma, and a favorable response was observed with radiologic disease stabilization, marked reductions in brain edema and requirement for corticosteroids, and improvement of clinical symptoms. However, treatment had to be discontinued after 5 cycles because of adverse drug effects.

CONCLUSIONS:

The current results indicated that trabectedin may represent a promising new therapeutic option for patients with aggressive meningioma and should be evaluated in prospective clinical studies. Cancer 2012. © 2012 American Cancer Society.

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