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Results of nimotuzumab and vinorelbine,radiation and re-irradiation for diffuse pontine glioma in childhood |
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| Authors: | Maura Massimino Veronica Biassoni Rosalba Miceli Elisabetta Schiavello Monika Warmuth-Metz Piergiorgio Modena Michela Casanova Emilia Pecori Felice Giangaspero Manila Antonelli Francesca Romana Buttarelli Paolo Potepan Bianca Pollo Raffaele Nunziata Filippo Spreafico Marta Podda Andrea Anichini Carlo Alfredo Clerici Iacopo Sardi Loris De Cecco Udo Bode Ferdinand Bach Lorenza Gandola |
| Affiliation: | 1. Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy 2. Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy 8. Department of Neuroradiology, University of Würzburg, Josef-Schneider-Str.11, 97080, Wurzburg, Germany 9. Genetics Unit, Pathology Department, Ospedale S. Anna, San Fermo della Battaglia, 22100, Como, Italy 3. Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy 10. Radiological and Oncological Sciences Department, Universita` Sapienza, Viale del Policlinico, 00151, Roma, Italy 11. Pathology Department, Universita` Sapienza, Viale del Policlinico, 00151, Roma, Italy 4. Radiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy 12. Neuropathology Unit, IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 20133, Milano, Italy 5. Human Tumor Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy 7. Physiopathology Department, State Medical School, Via Festa del Perdono, 20100, Milano, Italy 13. Neuro-Oncology Unit, Ospedale Meyer, Viale Pieraccini 24, 50139, Firenze, Italy 6. Molecular Therapies Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy 14. Department of Pediatric Hematology/Oncology, University of Bonn Medical School, Bonn, Germany 15. Oncoscience AG, Hafenstra?e 32, 22880, Wedel, Germany |
| 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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