Nimotuzumab y radioterapia en el tratamiento de tumores del tallo cerebral en niños y adolescentes

Jose Alert Silva, Ivon Chon Rivas, Ramon Ropero Toirac, Jose Valdes Marin, Jesus Reno Cespedes, Migdalia Perez Trejo, Mariuska Forteza Saez, Debora Garcia Socarras

Texto completo:

HTML

Resumen

Introducción: Los tumores localizados en el tallo cerebral en los niños y adolescentes conllevan un mal pronóstico, especialmente aquellos infiltrantes y difusos. Con el tratamiento de radioterapia apenas llegan a más de 15 % de supervivencia y no mejoran las cifras con quimioterapia agregada.
Objetivos: Estimar el efecto de la asociación del tratamiento radiante con el anticuerpo monoclonal Nimotuzumab en la supervivencia de niños y adolescentes con tumores del tallo cerebral
Método: Estudio clínico no aleatorizado, analítico, longitudinal y prospectivo en una serie de 46 pacientes entre 2 y 18 años de edad que padecían de tumores del tallo cerebral, infiltrantes y difusos, desde enero de 2008 y en seguimiento hasta marzo de 2018. Todos se trataron con radioterapia, con dosis entre 5400 y 5980 cGrey, dosis diaria de 18 cGrey,y e irradiados de lunes a viernes. Mientras duró el tratamiento radiante recibieron Nimotuzumab, en la dosis de 150 mg/m2 de superficie corporal, luego semanal con 8 dosis, y finalmente mensual durante uno o dos años.
Resultados: Se alcanzó en la serie una supervivencia media de 18,4 meses, y una esperada de 42,9 % a 2 años y 35,5 % a 5 años, estabilizada hasta los 10 años.
Conclusiones: La combinación de la radioterapia y el anticuerpo monoclonal Nimotuzumab incrementa la supervivencia en los tumores cerebrales del tallo cerebral en niños y adolescentes y es bien tolerada, aun en periodos prolongados, e incluso en casos de recidiva.

Referencias

Referencias Bibliograficas

-2016- Anuario Estadístico de Salud, Dirección de Registros Médicos y Estadísticos de la Salud, MINSAP, 95 ed.pp 103-104, Habana 2017.

– Blaney S, Kun I, Hunter J, Rorke-Adams C, Lai Ch, Strolter S et al. Tumors of Central Nervous System in: Pizzo P, Poplacked.Principles and Practice of Pediatric Oncology, 5th ed. Lippincott, Williams and Wilkins, Philadelphia, USA, 2006 pp 786-864.

–Wolff JE, Rytling ME, Vats TS, Zage PE, Ater J, Woo Sh et al. Treatment of recurrent diffuse intrinsic pontineglioma: the MD Anderson Cancer Center Experience. J Neurooncol 2012; 106:391-397.

–Gainar A, Packer RJ, Foresman NK, Cohen K, Haas-Kogan D, Merchant Th. Children´s Oncology Group´s 2013 Blueprint for Research: Central Nervous System Tumors. Pedrtr Blood Cancer 2013; 60:1021026.

–Massimino M, Beassoni V, Miceli R, Schiavelli E, Warmuth-Metz M, Modena P et al. Results of Nimotuzumab and Vinorelbine, radiation and re-irradiation for diffuse pontineglioma in childhood. J Neurooncol 2014; 118:305-312.

–Alert J, Chon I, Cabanas R, Reno J, Garcia D, Perez M and Ropero R. Radiation therapy and Nimotuzumab in children and adolescents with brainstem gliomas; a 5-year Institutional experience. Neuro open J 2015;2:45-50.

–Hargrave D, Bartels V, Bouffet F. Diffuse brainstem gliomas in children: critical review of clinical trials. Lancet Oncol 2006; 7:241-248.

–Combs SE, Steck I, Schulz-Estner D, Welzel TH, Kulozik A, Behnisch W et al. Long-term outcome of high-precision radiotherapy in patients with brainstem gliomas. Results from a difficult-to-treat population using fractionated stereotactic radiotherapy. RadiotherOncol 2009; 91:60-66.

–Frazier JL, Lee J, Thomale W, NoggieBS,Cohen KJ and Jallo G. Treatment of diffuse intrinsic braimstemgliomas. Failed approaches and future strategies. J Neurosurg: Pediatrics 2009; 3:259-269.

– Mac Donald TJ, Aguilera D, Kranm C. Treatment of high grade glioma in children and adolescents. Neurooncol 2011; 13: 1049-1058.

–Jansen GO, Gidding CE, Van Lindert EJ, Oldenburger FR, Erasmus CE, Schoutin-Meeterin A, et al. The role of hypofractionation radiotherapy for diffuse intrinsic brainstem gliomas in children: a pilot study. Int J RadiatOncolBiolPhys 2009; 73Ñ722-726.

–Negretti L, Boucireb K, Levy-Piedbois C, Habrand JL, Dhermain F, KalifaCh et al. Hypofractionated radiotherapy in the treatment of diffuse intrinsic pontineglioma in children: a single institution experience. J Neurooncol 2011;104:773-777.

–Marcus K, Dutton SH, Barnes P. A phase I trial of Etanidazole and hyperfractionated radiotherapy in children with diffuse brainstem gliomas. Int J RadiatOncolBiol Phys 2003;55:1182-1185.

–Jansen MH, Van Vuurden DG, Vaandertop WP, Kaspers GJ. Diffuse intrinsic pontinegliomas: a systemic update of clinical trials and biology. Cancer Treat Rev 2012; 38Ñ27-35.

–Zagloul M, Eldebarry,E, Ahmed S, Mousa A, Amin A, Zaky I et al. Hypoifractionated conformal radiotherapy for pediatric diffuse intrinsic pontineglioma ( DIPG ); a randomized controlled trial. RadiotherOncol 2014; 111:35-40.

–Veldhuijzen van Zauten SEM, Jansen MHA, Sanchez-Aliaga E, Van Vuurden W, Vandertop P, Kaspers GJ. A twenty year review of diagnosis and treating children with diffuse intrinsic pontineglioma in the Netherlands. Expert Rev Anticancer Ther 2015;15: 157-174.

–Veldhuijzen van Zautem SEM, El-Khouly F, Jansen M, Bakker D, Sanchez-Aliaga E, Haasbeek C et al. A phase I-II Study of gencitabine during radiotherapy in children with newly diagnosed diffuse intrinsic pontineglioma. J Neurooncol 2017; 135:307-315.

–Hassan H, Pinches A, Picton S, Phillips R.Survival rates and prognostic predictors of high grade brainstem gliomas in childhood a systemic review and meta-analysis. J Neurooncol 2017; 135:13-20.

–Massimino M, Bode U, Biassoni V, Fleichhack G. Nimotuzumab of pediatric diffuse intrinsic pontine gliomas. Expert Open Biol Ther 2011; 11: 247-256.

– Cabanas R, Saurez G, Rios M, Alert J, Reyes A, Valdes J et al. Treatment of children with high grade glioma with Nimotuzumab. A 5 year institutional experience. mAbs2013;5:202-207.

– Rivera F, Vega-Villegas ME, Lopez-Brea MF ,Marquez R. Current situation of Pantumumab, Matuzumab, Nimotuzumab and Zalutumumab Acta Oncol 2008; 47:9-19.

– Lam M, Bouffet F, Bartels J.Nimotuzumab in pediatric glioma. Future Oncol 2009; 9:1349-1361.

–Buczkowicz P, Bartels U, Bouffet E, Becher O, Hawkins C. Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications. Acta Neuropàthol 2014; 128:573-581.

–Minturn JE, Fisher MJ. Gliomas in children. Current Treat Options Neurol 2013; 15:316-327.

–Dellaretti M, Ryns N, Touzet G, Dubois F, Gusmao S, Pereira JBL, Blood S. Diffuse brainstem glioma: prognostic factors. J Neusosurg 2012; 117: 810-814.

–Cabanas R,Crombet T, Alert J,Valdes J, Gonzalez V, Pedrayes J et al. Nimotuzumab and Radiotherapy in children and adolescents with brainstem tumor: a phase II study. Pediatr Blood Cancer 2009;59:830-831.

–Cabanas R, Saurez G, Crombet T, Reyes A, Alert J, Valdes J et al. Saffety and efficacy results of the children and adolescents with Central Nervous System tumor. Nimotuzumab expended acces Program PM 042. Pediatr Blood Cancer 2011; 57:705-827.

–Cabanas R, Saurez G, Crombet T, Valdes J, Gonzalez MC, Pedrayes J et al. Saffety and efficacy of Nimotuzumab in the treatment of children and adolescents with Malignant Central Nervous System tumor. Peditr Blood Cancer 2012; 59. PMO59:965-1152.

–Cabanas R, Saurez G, Alert J, Reyes A, Gonzalez MC, Pedaryes J et al. Prolonged use of Nimotuzumab in children with Central Nervous tumor. Saffety and feasibility. Cancer Bioth and Radiopharm 2014; 29: 17178.

–Boland WK, Bebb G. Expert Opinion. Nimotuzumab, a novel anti EGFR monoclonal antibody that retains antEGFR activite while minimizing skin toxicity. Expert Opini Biol Ther 2009; 9:1199-1206

–Garrido G, Tikhomitov IA, Rabasa A, Yang E, Gracia E, Iznaga N et al. Bivalent binding by intermediate affinity of Nimotuzumab: a contribution to explain antibody clinical profile. Cancer Bio Ther 2011; 11:373-382.

–Boden WK, Bebb G. Expert opinion. Nimotuzumab, a novel anti EGFR monoclonal antibody that retains anti EGFR activite while minimizing skin toxicity. Expert Opin Biol Ther 2009; 0:1199-1206.

–Solomon MT, Selve JC, Figueredo J, Vequer J, Toledo C, Quintanal N et al. Nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized doublé blind trial BMC 2019:299 doi:10.1186/1471-2407-13.299.

–Alert J, Reno J, Garcia D, Saurez G. Three-dimensional conformal radiotherapy concurrent with chemotherapy and Nimotuzumab in the treatment of Head and Neck cáncer in children and adolescents: experience in a single institution. Ped Blood Cancer 2012; 59:94.

–Broniscer A, Laningham FH, Sanders RP, Kun LE, Ellison DW, Gajjar A. Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 2008; 113:566-572.

–Bartels U, Wolff J, Gore L, Dunkel I, Gilheeney S, Allen J et al. Phae 2 study of safety and efficacy of Nimotuzumab in pediatric patients with progressive diffuse intrinsic pontine glioma. Neuro Oncol 2014; 16:1554-1559.

Enlaces refback

  • No hay ningún enlace refback.




Copyright (c) 2018 Jose Alert Silva, Ivon Chon Rivas, Ramon Ropero Toirac, Jose Valdes Marin, Jesus Reno Cespedes, Migdalia Perez Trejo, Mariuska Forteza Saez, Debora Garcia Socarras

Licencia de Creative Commons
Este obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.