Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood.
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.
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy. maura.massimino@istitutotumori.mi.it.
Maura
M
Massimino
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Veronica
V
Biassoni
Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Rosalba
R
Miceli
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Elisabetta
E
Schiavello
Department of Neuroradiology, University of Würzburg, Josef-Schneider-Str.11, 97080, Wurzburg, Germany.
Monika
M
Warmuth-Metz
Genetics Unit, Pathology Department, Ospedale S. Anna, San Fermo della Battaglia, 22100, Como, Italy.
Piergiorgio
P
Modena
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Michela
M
Casanova
Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Emilia
E
Pecori
Radiological and Oncological Sciences Department, Universita` Sapienza, Viale del Policlinico, 00151, Roma, Italy.
Felice
F
Giangaspero
Radiological and Oncological Sciences Department, Universita` Sapienza, Viale del Policlinico, 00151, Roma, Italy.
Manila
M
Antonelli
Pathology Department, Universita` Sapienza, Viale del Policlinico, 00151, Roma, Italy.
Francesca Romana
FR
Buttarelli
Radiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Paolo
P
Potepan
Neuropathology Unit, IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 20133, Milano, Italy.
Bianca
B
Pollo
Neuropathology Unit, IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 20133, Milano, Italy.
Raffaele
R
Nunziata
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Filippo
F
Spreafico
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Marta
M
Podda
Human Tumor Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Andrea
A
Anichini
Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.|Physiopathology Department, State Medical School, Via Festa del Perdono, 20100, Milano, Italy.
Carlo Alfredo
CA
Clerici
Neuro-Oncology Unit, Ospedale Meyer, Viale Pieraccini 24, 50139, Firenze, Italy.
Iacopo
I
Sardi
Molecular Therapies Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Loris
L
De Cecco
Department of Pediatric Hematology/Oncology, University of Bonn Medical School, Bonn, Germany.
Udo
U
Bode
Oncoscience AG, Hafenstraße 32, 22880, Wedel, Germany.
Ferdinand
F
Bach
Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milano, Italy.
Lorenza
L
Gandola
D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D020295:Brain Stem Neoplasms / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D010865:Pilot Projects; D019233:Retreatment; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine
D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D007155:Immunologic Factors; D014747:Vinblastine; C501466:nimotuzumab; D000077235:Vinorelbine