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.