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Temozolomide and 13-cis retinoic acid in patients with anaplastic gliomas: a prospective single-arm monocentric phase-II study (RNOP-05)

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An Erratum to this article was published on 20 October 2011

Abstract

The objective of this prospective, monocentric phase-II pilot study was to evaluate toxicity and efficacy of neoadjuvant temozolomide (TMZ) and 13-cis retinoic acid (13-cRA) treatment in patients with newly diagnosed anaplastic gliomas after total or subtotal tumor resection. The primary endpoint of the study was median progression-free survival (PFS). Secondary endpoints were toxicity and PFS rates at 6, 12 and 24 months. Thirty-two adult patients were included in the study and treated with a median number of 10 TMZ and 13-cRA cycles (range 1–26). The majority of patients had favorable prognostic factors characterized by young age, complete resection, oligodendroglial histology, 1p/19q co-deletion, O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation and isocitrate dehydrogenase 1 (IDH1) mutation. Grade 3/4 myelotoxicity occurred in 5/32 patients, and about 90% of patients suffered from grade 2/3 adverse events attributable to 13-cRA. The median PFS was 37.8 months (95% CI 22.2–53.4). The 6-, 12- and 24-month PFS rates were 84.4, 75 and 42.4%. The extent of tumor resection was the only prognostic factor associated with better PFS. TMZ and 13-cRA treatment did not improve PFS when retrospectively compared to the TMZ-treated group within the randomized NOA-04 phase-III trial. In conclusion, 13-cRA addition to TMZ in a neoadjuvant setting showed acceptable toxicity, but did not yield an advantage in PFS in patients with newly diagnosed anaplastic gliomas after total or subtotal tumor resection.

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Acknowledgments

We cordially thank Birgit Hirschmann and Christiane Reinert for compiling the data for this analysis. We further thank Christel Herold-Mende and Benito Campos from the Department of Neurosurgery, University of Heidelberg, for analysing the retinoic acid signalling pathway expression in our dataset.

Funding

The study was supported by Essex Pharma (Schering-Plough Germany) with an unrestricted educational grant.

Conflict of interest

Ulrich Bogdahn: travel support by Schering-Plough; scientific advisor and speaker for Schering-Plough. Peter Hau: travel support by Schering-Plough; scientific advisor and speaker for Schering-Plough; several unrestricted educational grants by Schering-Plough. Wolfgang Wick: travel support by Schering-Plough; scientific advisor and speaker for Schering-Plough. Michael Weller: travel support by Schering-Plough; scientific advisor and speaker for Schering-Plough.

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Authors and Affiliations

  1. Department of Neurology, University Medical Center Regensburg, Universitätsstrasse 84, 93053, Regensburg, Germany

    Oliver Grauer, Christina Pascher, Ulrich Bogdahn & Peter Hau

  2. Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center, Heidelberg, Germany

    Christian Hartmann

  3. Department of Neuropathology, Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany

    Christian Hartmann

  4. Center for Clinical Studies, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Florian Zeman

  5. Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland

    Michael Weller

  6. Department of Neurosurgery, University Medical Center Regensburg, Franz-Josef-Strauß Allee 11, 93053, Regensburg, Germany

    Martin Proescholdt & Alexander Brawanski

  7. Department of Neuropathology, University of Bonn, Sigmund-Freud-Str. 3, 53015, Bonn, Germany

    Thorsten Pietsch

  8. Department of Neurooncology, Neurology Clinic and National Center for Tumor Disease, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Wolfgang Wick

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  1. Oliver Grauer
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Correspondence to Peter Hau.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s11060-011-0742-y

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Grauer, O., Pascher, C., Hartmann, C. et al. Temozolomide and 13-cis retinoic acid in patients with anaplastic gliomas: a prospective single-arm monocentric phase-II study (RNOP-05). J Neurooncol 104, 801–809 (2011). https://doi.org/10.1007/s11060-011-0548-y

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  • DOI: https://doi.org/10.1007/s11060-011-0548-y

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