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Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood

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A Correction to this article was published on 16 May 2018

Abstract

Radiotherapy is the only treatment definitely indicated for diffuse pontine gliomas (DIPG). Findings on the role of EGFR signaling in the onset of childhood DIPG prompted the use of nimotuzumab, an anti-EGFR monoclonal antibody. Assuming a potential synergy with both radiotherapy and vinorelbine, a pilot phase 2 protocol was launched that combined nimotuzumab with concomitant radiation and vinorelbine. An amendment in July 2011 introduced re-irradiation at relapse. The primary endpoint for first-line treatment was objective response rate (CR + PR + SD) according to the RECIST. This report concerns the outcome of this strategy as a whole. Vinorelbine 20 mg/m2 was administered weekly, with nimotuzumab 150 mg/m2 in the first 12 weeks of treatment; radiotherapy was delivered from weeks 3 to 9, for a total dose of 54 Gy. Vinorelbine 25 mg/m2 and nimotuzumab were given every other week thereafter until the tumor progressed or for up to 2 years. Re-irradiation consisted of 19.8 Gy, fractionated over 11 days. Baseline and latest MRIs were assessed blindly by an outside neuroradiologist. Twenty five children (mean age 7.4 years) were enrolled as of August 2009 (median follow-up 29 months). A response was observed in 24/25 patients (96 %). The nimotuzumab/vinorelbine combination was very well tolerated, with no acute side-effects. Eleven of 16 locally-relapsing patients were re-irradiated. One-year PFS and OS rates were 30 ± 10 % and 76 ± 9 %, respectively; 2-year OS was 27 ± 9 %; the median PFS and OS were 8.5 and 15 months, respectively. This strategy generated interesting results and warrants further investigation.

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Acknowledgments

This work was supported by the Associazione Bianca Garavaglia Onlus (Busto Arsizio Italy), the Fondo di Giò Onlus (Trieste, Italy), and the Associazione Italiana per la Ricerca Sul Cancro (AIRC); nimotuzumab was given on compassionate grounds by Oncoscience AG.

Conflict of interest

There are no other conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy

    Maura Massimino, Veronica Biassoni, Elisabetta Schiavello, Michela Casanova, Filippo Spreafico, Marta Podda & Carlo Alfredo Clerici

  2. Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy

    Rosalba Miceli

  3. Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy

    Emilia Pecori & Lorenza Gandola

  4. Radiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy

    Paolo Potepan

  5. Human Tumor Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy

    Andrea Anichini

  6. Molecular Therapies Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy

    Loris De Cecco

  7. Physiopathology Department, State Medical School, Via Festa del Perdono, 20100, Milano, Italy

    Carlo Alfredo Clerici

  8. Department of Neuroradiology, University of Würzburg, Josef-Schneider-Str.11, 97080, Wurzburg, Germany

    Monika Warmuth-Metz

  9. Genetics Unit, Pathology Department, Ospedale S. Anna, San Fermo della Battaglia, 22100, Como, Italy

    Piergiorgio Modena

  10. Radiological and Oncological Sciences Department, Universita` Sapienza, Viale del Policlinico, 00151, Roma, Italy

    Felice Giangaspero & Manila Antonelli

  11. Pathology Department, Universita` Sapienza, Viale del Policlinico, 00151, Roma, Italy

    Francesca Romana Buttarelli

  12. Neuropathology Unit, IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 20133, Milano, Italy

    Bianca Pollo & Raffaele Nunziata

  13. Neuro-Oncology Unit, Ospedale Meyer, Viale Pieraccini 24, 50139, Firenze, Italy

    Iacopo Sardi

  14. Department of Pediatric Hematology/Oncology, University of Bonn Medical School, Bonn, Germany

    Udo Bode

  15. Oncoscience AG, Hafenstraße 32, 22880, Wedel, Germany

    Ferdinand Bach

Authors
  1. Maura Massimino
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  21. Udo Bode
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  22. Ferdinand Bach
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  23. Lorenza Gandola
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Corresponding author

Correspondence to Maura Massimino.

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Massimino, M., Biassoni, V., Miceli, R. et al. Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neurooncol 118, 305–312 (2014). https://doi.org/10.1007/s11060-014-1428-z

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  • DOI: https://doi.org/10.1007/s11060-014-1428-z

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