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Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

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Abstract

Purpose

Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma.

Methods

Patients with recurrent or progressive WHO grade I–III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18–75 years, ECOG performance status 0–2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9).

Results

Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75 %, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75 %, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0.

Conclusion

The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

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Acknowledgments

This study was in part supported by two unrestricted Grants (Grants Number: not applicable) from GICNO and from Novartis which were used for trial conduction costs. Glivec was supplied by Novartis, Italy. Novartis did not have any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit paper for publication.

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Authors and Affiliations

  1. Medical Oncology Unit, Department of Oncology, IRCCS Ospedale, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy

    Elena Mazza, Silvia Zanon & Michele Reni

  2. Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL of Bologna - IRCCS Institute of Neurological Sciences, Bologna, Italy

    Alba Brandes & Enrico Franceschi

  3. Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy

    Marika Eoli

  4. Department of Experimental and Clinical Oncology, Medical Oncology 1, Veneto Institute of Oncology-IRCCS, Padua, Italy

    Giuseppe Lombardi

  5. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Marina Faedi

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  1. Elena Mazza
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  2. Alba Brandes
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Correspondence to Michele Reni.

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Mazza, E., Brandes, A., Zanon, S. et al. Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Cancer Chemother Pharmacol 77, 115–120 (2016). https://doi.org/10.1007/s00280-015-2927-0

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  • DOI: https://doi.org/10.1007/s00280-015-2927-0

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