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

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/m(2) was administered weekly, with nimotuzumab 150 mg/m(2) 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/m(2) 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.

Pre-radiation chemotherapy improves survival in pediatric diffuse intrinsic pontine gliomas

“…These disappointing survival results are confirmed in several recent reviews of the literature about the targeted therapies that are tested in these new trials [5][6][7][8][9]14]. However, a pilot phase II protocol which combined nimotuzumab (an anti-EGFR monoclonal antibody) with concomitant radiation and vinorelbine has shown encouraging results in median PFS and OS (8.5 and 15 months, respectively) [38]. These results, as well as ours, prove that chemotherapy and targeted therapies are of interest in the management of DIPG.…”

Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition

“…This toxicity in laboratory animals can be mitigated by co-administration of glucocorticoids (40, 41). Radiation therapy is the initial treatment for DIPG, and reirradiation is increasingly being used in patients with relapses (42). Most of these patients receive dexamethasone to mitigate the cerebral edema associated with their tumor and radiation.…”

Recent advances and future of immunotherapy for glioblastoma

“…Intra-arterial infusion of cetuximab alone or in combination with BEV is currently being tested 154 (NCT01884740 and NCT01238237). Another antibody against EGFR, nimotuzumab, in combination with radiation and chemotherapy in patients with diffuse intrinsic pontine gliomas has shown an increased median OS of 15 months when compared to 9.4 months for nimotuzumab and radiation alone 155 . A randomised, open label phase III trial was conducted to evaluate efficacy of nimotuzumab added to standard therapy for newly diagnosed glioblastoma.…”